A disproportionate incidence's increase of rectal cancer in patients younger than 50 years of age. The ESMO and NCCN recommendations are not age-specific and the literature is poor and conflicting. We decided to examine patients with rectal cancer treated in our centre in the last 15 years with curative neoadjuvant radiochemotherapy comparing outcomes in the two groups under and over 55 years old.

788 rectal cancer patients were enrolled in this monocentric retrospective observational study (523 =>55 years and 265 < 55). All patients received neoadjuvant chemoradiation treatment. R statistical software v.4.1.3 was used for the entire analysis. The outcomes were death, local recurrence, and new distant metastases. Survival analysis was performed using the Kaplan-Meier method and the Log-rank was used to compare the two groups.

All patients were classified in different risk groups, according to the ESMO 2017 rectal cancer clinical practice guidelines. 88 % of patients under 55 years old at the diagnosis belonged to the bad or advanced risk groups with an equal division. In patients over 55 years old, there was a clear dominance of the advanced risk class (62 % of the total). In multivariate analysis, OS and DFS decrease with increasing age and ESMO risk group. The other variables in multivariate were not significant. For Both OS, DFS and MFS, the curves separated significantly at 55 years of age, with a prevalence of metastasis development in the older group.

Elderly patients have a prevalence of advanced disease. Younger patients seem having a better OS at 3 and 5 years. ESMO risk group and age were the only variables affecting OS and DFS. Young patients have better MFS and DFS at 2 and 5 years than patients older than 55 years. The addition of oxaliplatin to fluoropyrimidine-based neoadjuvant chemotherapy resulted not significant in both groups.

The 2024 updates of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China, highlighting the latest advancements in evidence-based medicine, healthcare resource access, and precision medicine in oncology. These updates address disparities in epidemiological trends, clinicopathological characteristics, tumor biology, treatment approaches, and drug selection for colorectal cancer patients across diverse regions and backgrounds. Key revisions include adjustments to evidence levels for intensive treatment strategies, updates to regimens for deficient mismatch repair (dMMR)/ microsatellite instability-high (MSI-H) patients, proficient mismatch repair (pMMR)/ microsatellite stability (MSS) patients who have failed standard therapies, and rectal cancer patients with low recurrence risk. Additionally, recommendations for digital rectal examination and DNA polymerase epsilon (POLE)/ DNA polymerase delta 1 (POLD1) gene mutation testing have been strengthened. The 2024 CSCO Guidelines are based on both Chinese and international clinical research, as well as expert consensus, ensuring their relevance and applicability in clinical practice, while maintaining a commitment to scientific rigor, impartiality, and timely updates.

The aim of the study is to assess whether transcatheter rectal arterial chemoembolization (TRACE) with oxaliplatin could increase the pathologic complete response (pCR) rate of locally advanced rectal cancer (LARC) and improve survival outcomes, while minimizing adverse events compared to preoperative chemoradiotherapy (CRT) alone.

Eligible LARC patients who received TRACE with oxaliplatin plus chemoradiotherapy (the NATRACE-CRT group) or preoperative CRT alone (the NA-CRT group) were retrospectively selected from the database of our institution. Pathological results, treatment-related adverse events and survival in the two groups were compared.

A total of 236 patients were enrolled. The pCR rates were 18.38 % in the NATRACE-CRT group and 14.00 % in the NA-CRT group, with a non-significant difference of 4.38 % (P = 0.473). The median follow-up time was 42 months. The 5-year DFS (75.7 % vs. 73.2 %; P = 0.879) and OS (73.4 % vs. 70.3 %; P = 0.855) rates were comparable between the NATRACE-CRT group and the NA-CRT group. However, the NATRACE-CRT group had significantly fewer patients achieving TRG3 compared to the NA-CRT group (16.18 % vs. 35.00 %; P = 0.001). Furthermore, TRG3 patients in the NATRACE-CRT group exhibited significantly longer OS compared to those in the NA-CRT group (5-year OS: 88.9 % vs 59.5 %; P = 0.016).

TRACE with oxaliplatin demonstrates potential in improving treatment response and prognosis of LARC patients with chemoradiotherapy resistance.

Current approaches for locally advanced rectal cancer (LARC) typically recommend neoadjuvant chemoradiotherapy (nCRT) with 5-fluorouracil (5FU) or its oral analogs followed by surgery as the standard of care. However, the question of whether intensifying concurrent chemotherapy by adding oxaliplatin to the 5FU-based backbone can yield better outcomes remains unresolved. This study aimed to investigate the benefits of incorporating oxaliplatin into fluoropyrimidine-based chemoradiotherapy (CRT) to increase locoregional control and survival.

Among 290 patients with LARC admitted to the Iran Cancer Institute's radiation oncology department between January 2008 and December 2019, 29 received CAPEOX (capecitabine 625 mg/m²/bid on RT days and weekly oxaliplatin 50 mg/m²), whereas 293 received capecitabine (825 mg/m² twice daily or rarely 5FU in the first 4 days and last week of radiotherapy (RT)). Variables potentially affecting treatment outcomes were used for propensity score matching. Kaplan‒Meier and log-rank tests were employed for overall survival (OS) and disease-free survival (DFS) analyses and were adjusted with propensity score matching.

Data from 29 patients who received CAPEOX and 216 patients who received capecitabine were analyzed after propensity score matching without replacement. After propensity score matching, in the multivariate analysis, CAPEOX significantly increased the likelihood of achieving a pathologic complete response (pCR) by 4.38 times (CI: 1.90-10.08, p value < 0.001). However, CAPEOX did not demonstrate any statistically significant predictive value for DFS (P = 0.500) or OS (P = 0.449).

The addition of oxaliplatin resulted in a significantly higher rate of pCR without any translation into long-term survival outcomes.

This study aimed to evaluate the effects of adjuvant chemotherapy (AC) on oncologic outcomes for patients with stage IIA upper rectal cancer and to investigate whether AC is associated with improved survival outcomes.

This retrospective study comprised 432 patients with rectal cancer above the peritoneal reflection who had undergone curative resection without preoperative chemoradiotherapy between 2008 and 2016. This study cohort was divided according to whether AC was received (AC group) or not (no-AC group). Risk factors included obstruction, perforation, poorly-differentiated tumor, lympho-vascular invasion, perineural invasion, resection margin involvement, and < 12 lymph nodes harvested.

Among the 432 patients, 279 (64.6%) had received AC. The AC group had significantly higher 5-year overall survival (OS) rates than those of the no-AC group (93.2% vs. 84.6%, P = .001). Among patients with ≥ 1 risk factors, the AC group (n = 123) had significantly higher rates of 5-year recurrence-free survival (RFS) (81.6% vs. 64.1%, P = .01) and 5-year OS (88.8% vs. 69.0%, P = .001) than those of the no-AC group (n = 59). No significant difference in survival outcomes was observed between the 2 groups in patients aged > 65 years.

AC was significantly associated with better 5-year RFS and 5-year OS rates in patients with stage IIA rectal cancer above peritoneal reflection who did not receive preoperative chemoradiotherapy, especially in those with ≥ 1 risk factors.

The PRODIGE-23 study showed a higher benefit for FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) as induction chemotherapy followed by long-course chemoradiotherapy (CTRT) respect to neoadjuvant CTRT alone both followed by total mesorectal excision (TME) in terms of disease-free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). The added value of treatment intensification with irinotecan, over the doublet induction with fluoropyrimidine and oxaliplatin is still debated.

To assess survival, pathological complete response (pCR) rate, and safety from phase II-III trials comparing triplet and doublet induction both followed by CTRT and TME in LARC.

After a systematic literature review of PubMed, Embase, Cochrane, American Society of Clinical Oncology and European Society for Medical Oncology meetings' libraries, data from Kaplan-Meier (KM) curves were extracted from phase II-III clinical trials. Phase II-III trials including at least one treatment arm with doublet or triplet induction chemotherapy without biological agents administered for a minimum of 3 months followed by long-course CTRT and TME and with at least 48 months of follow-up were selected. When available, the neoadjuvant CTRT alone arms of the selected studies were included as a comparator reference treatment. Individual patient DFS and OS data were extracted from Kaplan-Meier plots of original trials through graphical reconstruction between April 10th and May 19th, 2024. A pooled analysis was conducted, and results were validated in a subsequent network meta-analysis (NMA). pCR rates and grade ≥ 3 adverse events rates were also collected. Primary endpoints were DFS and OS between triplet and doublet induction. Secondary endpoints were DFS and OS between neoadjuvant CTRT alone and triplet or doublet induction as well as pCR rates and safety profile among different arms.

Out of 674 patients enrolled in 3 trials, 231, 161 and 282 were treated with FOLFIRINOX or CAPOX (capecitabine and oxaliplatin) followed by CTRT or neoadjuvant CTRT alone, respectively. 5-year DFS rates were 73.1 % [95 %CI: 67.2 % - 79.0 %], 61.7 % [95 %CI: 53.9 % - 69.5 %] and 65.1 % [95 %CI: 59.4 % - 70.8 %] for triplet induction, doublet induction, and neoadjuvant CTRT alone, respectively. 5-year OS rates were 86.8 % [95 %CI: 82.3 % - 91.3 %], 74.7 % [95 %CI: 67.6 % - 81.8 %], and 79.6 % [95 %CI: 74.9 % - 84.3 %] for FOLFIRINOX, CAPOX, and neoadjuvant CTRT alone, respectively. Triplet induction showed longer DFS and OS respect to doublet induction (HR for DFS: 0.67 [95 % CI 0.47 - 0.96], p = 0.03; HR for OS: 0.49 [95 % CI 0.31 - 0.78], p = 0.003) with a trend for superiority when compared with neoadjuvant CTRT alone (HR for DFS: 0.77 [95 % CI 0.57 - 1.05], p = 0.10; HR for OS: 0.67 [95 % CI 0.45 - 1.01], p = 0.06). No difference was observed between the doublet induction and neoadjuvant CTRT groups. pCR rates were higher for patients treated with FOLFIRINOX (27.7 %) respect to subjects receiving CAPOX (19.7 %, p = 0.02) or neoadjuvant CTRT alone (12.5 %, p < 0.0001). Triplet was associated with higher rates of severe neutropenia (17 % vs 1 %, p < 0.0001) and nausea-vomiting (11 % vs 3 %, p = 0.02) respect to doublet induction.

Induction with FOLFIRINOX showed better survival outcomes and pCR rates respect to CAPOX at the price of increased G3-4 neutropenia and nausea/vomiting. A randomized study comparing triplet and doublet chemotherapy in the frame of a total neoadjuvant treatment strategy is widely warranted.

Late diagnosis is considered one of the main reasons of high mortality rate among cancer patients that results in therapeutic failure and tumor relapse. Therefore, it is needed to evaluate the molecular mechanisms associated with tumor progression to introduce efficient markers for the early tumor detection among cancer patients. The remarkable stability of microRNAs (miRNAs) in body fluids makes them potential candidates to use as the non-invasive tumor biomarkers in cancer screening programs. MiR-135b has key roles in prognosis and survival of cancer patients by either stimulating or inhibiting cell proliferation, invasion, and angiogenesis. Therefore, in the present review we assessed the molecular biology of miR-135b during tumor progression to introduce that as a novel tumor marker in cancer patients. It has been reported that miR-135b mainly acts as an oncogene by regulation of transcription factors, signaling pathways, drug response, cellular metabolism, and autophagy. This review paves the way to suggest miR-135b as a tumor marker and therapeutic target in cancer patients following the further clinical trials and animal studies.

Background and Objectives: Conventional radiotherapies used in the current management of rectal cancer commonly cause iatrogenic radiotoxicity. Proton beam therapy has emerged as an alternative to conventional radiotherapy with the aim of improving tumour control and reducing off-set radiation exposure to surrounding tissue. However, the real-world treatment and oncological outcomes associated with the use of proton beam therapy in rectal cancer remain poorly characterised. This systematic review seeks to evaluate the radiation dosages and safety of proton beam therapy compared to conventional radiotherapy in patients with non-metastatic rectal cancer. Materials and Methods: A computer-assisted search was performed on the Medline, Embase and Cochrane Central databases. Studies that evaluated the adverse effects and oncological outcomes of proton beam therapy and conventional radiotherapy in adult patients with non-metastatic rectal cancer were included. Results: Eight studies were included in this review. There was insufficient evidence to determine the adverse treatment outcomes of proton beam therapy versus conventional radiotherapy. No current studies assessed radiotoxicities nor oncological outcomes. Pooled dosimetric comparisons between proton beam therapy and various conventional radiotherapies were associated with reduced radiation exposure to the pelvis, bowel and bladder. Conclusions: This systematic review demonstrates a significant paucity of evidence in the current literature surrounding adverse effects and oncological outcomes related to proton beam therapy compared to conventional radiotherapy for non-metastatic rectal cancer. Pooled analyses of dosimetric studies highlight greater predicted radiation-sparing effects with proton beam therapy in this setting. This evidence, however, is based on evidence at a moderate risk of bias and clinical heterogeneity. Overall, more robust, prospective clinical trials are required.

Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy (nCRT) for rectal cancer. However, the underlying mechanisms remain elusive.

To detect the differential expression profiles of plasma exosomal microRNAs (miRNAs) in poor and good responders and explore the potential mechanisms of chemoresistance.

In this study, the profiles of plasma exosomal miRNAs were compared in two dimensions according to treatment responses (poor/good responders) and treatment courses (pre/post-nCRT) using RNA sequencing.

Exosome hsa-miR-483-5p was up-regulated in good responders post-nCRT. Bioinformatics analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways, such as the MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, Toll-like receptor signaling pathway, VEGF signaling pathway, and mTOR signaling pathway. Further analysis indicated that MAPK3, RAX2, and RNF165 were associated with inferior recurrence-free survival in patients with rectal cancer, and the profiles of MAPK3, TSPYL5, and ZNF417 were correlated with tumor stage. In addition, the expression profiles of MAPK3, RNF165, and ZNF417 were negatively correlated with inhibitory concentration 50 values. Accordingly, an hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 network was constructed.

This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs. However, further research is required within the framework of our established miRNA-mRNA network.

To explore the diverse profiles of adverse reactions caused by oxaliplatin between colon and rectal cancer, we investigated the toxicity of oxaliplatin in patients with colon and rectal cancer.

From January 2017 to December 2021, 200 cases of sporadic CRC patients with adverse reactions after oxaliplatin were collected from Harbin Medical University Cancer Hospital, Harbin, China. All patients received a chemotherapy regimen containing oxaliplatin (100 colon cancer and 100 rectal cancer). We reviewed the adverse reactions induced by oxaliplatin in patients with colon and rectal cancer.

We found there was no significant difference in gastrointestinal toxicity, hematotoxicity, neurotoxicity, hepatotoxicity, respiratory toxicity, and cardiotoxicity caused by oxaliplatin between patients with colon cancer and patients with rectal cancer, but patients with rectal cancer were more prone to allergic reactions than patients with colon cancer after oxaliplatin. In addition, we found neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) were higher in patients with colon cancer than in patients with rectal cancer. This may reflect differences in immune status and inflammatory responses between colon cancer and rectal cancer, which might be the reason for more allergic reactions caused by oxaliplatin in colon cancer patients compared to rectal cancer patients.

Except for a higher incidence of allergic reactions in patients with rectal cancer, no significant difference in the incidence of adverse drug reactions associated with oxaliplatin was noted between patients with colon cancer and rectal cancer. Our results suggested more attention should be paid to the allergic reaction caused by oxaliplatin in patients with colon cancer.

This study evaluated pretreatment magnetic resonance imaging (MRI)-detected extramural venous invasion (pmrEMVI) as a predictor of survival after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).

Medical records of 1184 patients with rectal adenocarcinoma who underwent TME between January 2011 and December 2016 were reviewed. MRI data were collected from a computerized radiologic database. Cox proportional hazards analysis was used to assess local, systemic recurrence, and disease-free survival risk based on pretreatment MRI-assessed tumor characteristics. After propensity score matching (PSM) for pretreatment MRI features, nCRT therapeutic outcomes according to pmrEMVI status were evaluated. Cox proportional hazards analysis was used to identify risk factors for early recurrence in patients receiving nCRT.

Median follow-up was 62.8 months. Among all patients, the presence of pmrEMVI was significantly associated with worse disease-free survival (DFS; HR 1.827, 95% CI 1.285-2.597, p = 0.001) and systemic recurrence (HR 2.080, 95% CI 1.400-3.090, p < 0.001) but not local recurrence. Among patients with pmrEMVI, nCRT provided no benefit for oncological outcomes before or after PSM. Furthermore, pmrEMVI( +) was the only factor associated with early recurrence on multivariate analysis in patients receiving nCRT.

pmrEMVI is a poor prognostic factor for DFS and SR in patients with non-metastatic rectal cancer and also serves as a predictive biomarker of poor DFS and SR following nCRT in LARC. Therefore, for patients who are positive for pmrEMVI, consideration of alternative treatment strategies may be warranted.

This study demonstrated the usefulness of pmrEMVI as a predictive biomarker for nCRT, which may assist in initial treatment decision-making in patients with non-metastatic rectal cancer.

• Pretreatment MRI-detected extramural venous invasion (pmrEMVI) was significantly associated with worse disease-free survival and systemic recurrence in patients with non-metastatic rectal cancer. • pmrEMVI is a predictive biomarker of poor DFS following nCRT in patients with LARC. • The presence of pmrEMVI was the only factor associated with early recurrence on multivariate analysis in patients receiving nCRT.

Total neoadjuvant therapy (TNT) is a novel strategy for rectal cancer that administers both (chemo)radiotherapy and systemic chemotherapy before surgery. TNT is expected to improve treatment compliance, tumor regression, organ preservation, and oncologic outcomes. Multiple TNT regimens are currently available with various combinations of the treatments including induction or consolidation chemotherapy, triplet or doublet chemotherapy, and long-course chemoradiotherapy or short-course radiotherapy. Evidence on TNT is rapidly evolving with new data on clinical trials, and no definitive consensus has been established on which regimens to use for improving outcomes. Clinicians need to understand the advantages and limitations of the available regimens for multidisciplinary decision making. This article reviews currently available evidence on TNT for rectal cancer. A decision making flow chart is provided for tailor-made use of TNT regimens based on tumor location and local and systemic risk.

The PCAR study aimed to assess the efficacy and safety of preoperative transcatheter rectal arterial chemoembolisation (TRACE) in patients with locally advanced rectal cancer (LARC).

This was a single-centre, prospective, phase II trial conducted in China. Eligible patients were adults aged 18 years and older with histologically confirmed stage II or III rectal carcinoma and an Eastern Cooperative Oncology Group performance status of 0-1. Patients received TRACE with oxaliplatin, followed by radiotherapy with a cumulative dose of 45 Gy (1.8 Gy/time/day, five times a week for 5 weeks) and received oral S1 capsules twice daily (7 days a week for 4 weeks). Patients underwent total mesorectal excision 4-8 weeks after the completion of chemoradiotherapy, followed by mFOLFOX6 or CAPOX regimens for 4-6 months. The hypothesis of this study was that adding TRACE to preoperative neoadjuvant chemoradiotherapy would improve tumour regression and prognosis. The primary end point was the pathological complete response rate; secondary end points included the major pathological response rate, anal preservation rate, 5-year disease-free survival (DFS), 5-year overall survival and treatment-related adverse events.

In total, 111 LARC patients received TRACE and subsequent scheduled treatment plans. The pathological complete response and major pathological response rates were 20.72% and 48.65%, respectively. The 5-year DFS and 5-year overall survival were 61.89% (95% confidence interval 51.45-74.45) and 74.80% (95% confidence interval 65.05-86.01), respectively. Grade 3-4 toxicities were reported in 29 patients (26.13%). The postoperative complication rate was 21.62%, without serious surgical complications. Multivariate Cox regression analysis showed that ypN stage (hazard ratio = 4.242, 95% confidence interval 2.101-8.564, P = 0.00017) and perineural invasion (hazard ratio = 2.319, 95% confidence interval 1.058-5.084, P = 0.0487) were independent risk factors associated with DFS, whereas ypN stage (hazard ratio = 3.164, 95% confidence interval 1.347-7.432, P = 0.0101), perineural invasion (hazard ratio = 4.118, 95% confidence interval 1.664-10.188, P = 0.0134) and serum carbohydrate antigen 199 (CA199; hazard ratio = 4.142, 95% confidence interval 1.290-13.306, P = 0.0344) were independent predictors for overall survival.

The current study provides evidence that adding TRACE to neoadjuvant chemoradiotherapy can improve the pathological remission rate in LARC patients with acceptable toxicity. Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with LARC should be considered.

Neoadjuvant chemoradiotherapy has emerged as the established treatment for locally advanced rectal cancer. Nevertheless, there remains a debate regarding the necessity of adjuvant chemotherapy for patients with locally advanced rectal cancer who exhibit a favorable tumor response (ypT0-2N0) after neoadjuvant chemoradiotherapy and surgery. Thus, the objective of this study is to investigate the impact of adjuvant chemotherapy on the oncological prognosis of rectal cancer patients who have a good response to neoadjuvant chemoradiotherapy.

The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Articles were searched in the Web of Science, PubMed, and Cochrane Library databases. The primary outcomes assessed were 5-year overall survival, disease-free survival, cancer-specific survival, recurrence-free survival, local recurrence, and distant metastasis. The data was summarized using a random effects model.

A meta-analysis was conducted using 18 retrospective studies published between 2009 and 2023. The studies included 9 from China and 5 from Korea, involving a total of 6566 patients with ypT0-2N0 rectal cancer after neoadjuvant chemoradiotherapy. The pooled data revealed that adjuvant chemotherapy significantly improved 5-year overall survival (OR=1.75, 95% CI: 1.15-2.65, P=0.008), recurrence-free survival (OR=1.73, 95% CI: 1.20-2.48, P=0.003), and reduced distant metastasis (OR=0.68, 95% CI: 0.51-0.92, P=0.011). However, adjuvant chemotherapy did not have a significant effect on disease-free survival, cancer-specific survival, and local recurrence in ypT0-2N0 rectal cancer. Subgroup analysis indicated that adjuvant chemotherapy was beneficial in improving overall survival for ypT1-2N0 rectal cancer (OR=1.89, 95% CI: 1.13-3.19, P=0.003).

The findings of the meta-analysis suggest that adjuvant chemotherapy may provide benefits in terms of oncological outcomes for rectal cancer patients with ypT0-2N0 after neoadjuvant chemoradiotherapy and radical surgery. However, further prospective clinical studies are needed to confirm these findings.

Randomised controlled trials (RCTs) continue to provide the best evidence for treatment options, but the quality of reporting in RCTs and the completeness rate of reporting of surgical outcomes and complication data vary widely. The aim of this study was to measure the quality of reporting of the surgical outcome and complication data in RCTs of rectal cancer treatment and whether this quality has changed over time.

Eligible articles with the keywords ("rectal cancer" OR "rectal carcinoma") AND ("radiation" OR "radiotherapy") that were RCTs and published in the English, German, Polish, or Italian language were identified by reviewing all abstracts published from 1982 through 2022. Two authors independently screened and analysed all studies. The quality of the surgical outcome and complication data was assessed based on fourteen criteria, and the quality of RCTs was evaluated based on a modified Jadad scale. The primary outcome was the quality of reporting in RCTs and the completeness rate of reporting of surgical results and complication data.

A total of 340 articles reporting multimodal therapy outcomes for 143,576 rectal cancer patients were analysed. A total of 7 articles (2%) met all 14 reporting criteria, 13 met 13 criteria, 27 met from 11 to 12 criteria, 36 met from 9 to 10 criteria, 76 met from 7 to 8 criteria, and most articles met fewer than 7 criteria (mean 5.5 criteria). Commonly underreported criteria included complication severity (15% of articles), macroscopic integrity of mesorectal excision (17% of articles), length of stay (18% of articles), number of lymph nodes (21% of articles), distance between the tumour and circumferential resection margin (CRM) (26% of articles), surgical radicality according to the site of the primary tumour (R0 vs. R1 + R2) (29% of articles), and CRM status (38% of articles).

Inconsistent surgical outcome and complication data reporting in multimodal rectal cancer treatment RCTs is standard. Standardised reporting of clinical and oncological outcomes should be established to facilitate comparing studies and results of related research topics.

Patients with rectal cancer without distant metastases are typically treated with radical surgery. Post curative resection, several factors can affect tumor recurrence. This study aimed to analyze factors related to rectal cancer recurrence after curative resection using different machine learning techniques.

Consecutive patients who underwent curative surgery for rectal cancer between 2004 and 2018 at Gil Medical Center were included. Patients with stage IV disease, colon cancer, anal cancer, other recurrent cancer, emergency surgery, or hereditary malignancies were excluded from the study. The Synthetic Minority Oversampling Technique with Tomek link (SMOTETomek) technique was used to compensate for data imbalance between recurrent and no-recurrent groups. Four machine learning methods, logistic regression (LR), support vector machine (SVM), random forest (RF), and Extreme gradient boosting (XGBoost), were used to identify significant factors. To overfit and improve the model performance, feature importance was calculated using the permutation importance technique.

A total of 3320 patients were included in the study. After exclusion, the total sample size of the study was 961 patients. The median follow-up period was 60.8 months (range:1.2-192.4). The recurrence rate during follow-up was 13.2% (n = 127). After applying the SMOTETomek method, the number of patients in both groups, recurrent and non-recurrent group were equalized to 667 patients. After analyzing for 16 variables, the top eight ranked variables {pathologic Tumor stage (pT), sex, concurrent chemoradiotherapy, pathologic Node stage (pN), age, postoperative chemotherapy, pathologic Tumor-Node-Metastasis stage (pTNM), and perineural invasion} were selected based on the order of permutational importance. The highest area under the curve (AUC) was for the SVM method (0.831). The sensitivity, specificity, and accuracy were found to be 0.692, 0.814, and 0.798, respectively. The lowest AUC was obtained for the XGBoost method (0.804), with a sensitivity, specificity, and accuracy of 0.308, 0.928, and 0.845, respectively. The variable with highest importance was pT as assessed through SVM, RF, and XGBoost (0.06, 0.12, and 0.13, respectively), whereas pTNM had the highest importance when assessed by LR (0.05).

In the current study, SVM showed the best AUC, and the most influential factor across all machine learning methods except LR was found to be pT. The rectal cancer patients who have a high pT stage during postoperative follow-up are need to be more close surveillance.

Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT).

A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness.

This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness.

This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.

Postoperative adjuvant chemotherapy (AC) for poor responders to neoadjuvant chemoradiotherapy (nCRT) remains debatable among patients with locally advanced rectal cancer (LARC), necessitating biomarkers to accurately predict the benefits of AC. This study aimed to develop a patient-derived tumor organoid (PDTO) platform to predict the benefit of AC in LARC patients showing poor nCRT response. PDTOs were established using irradiated rectal cancer specimens with poor nCRT responses, and their sensitivity to chemotherapy regimens was tested. The half-maximal inhibitory concentration (IC50) value for the PDTO drug test was defined based on the clinical outcomes, and the accuracy of the PDTO prognostic predictions was calculated. Predictive models were developed and validated using the PDTO drug test results. Between October 2018 and December 2021, 86 PDTOs were successfully constructed from 138 specimens (success rate 62.3%). The optimal IC50 cut-off value for the organoid drug test was 39.31 μmol/L, with a sensitivity of 84.75%, a specificity of 85.19%, and an accuracy of 84.88%. Multivariate Cox regression analysis revealed that the PDTO drug test was an independent predictor of prognosis. A nomogram based on the PDTO drug test was developed, showing good prognostic ability in predicting the 2-year and 3-year disease-free survivals (AUC of 0.826 [95% CI, 0.721-0.931] and 0.902 [95% CI, 0.823-0.982], respectively) and overall survivals (AUC of 0.859 [95% CI, 0.745-0.973] and 0.885 [95% CI, 0.792-0.978], respectively). The PDTO drug test can predict the benefit of postoperative AC in poor responders with LARC to nCRT.

/Objective: To compare the prognostic value of the yield pathologic (yp) stage, used 4 tumor regression grading (TRG) systems, and neoadjuvant rectal score(NARS) in patients with locally advanced rectal cancer (LARC) who received long-term neoadjuvant chemoradiotherapy (nCRT).

Between 2005 and 2017, we included 302 patients with LARC who treated with nCRT. Postoperative pathological responses were graded by using Dworak, American Joint Committee on Cancer, Mandart, Memorial Sloan Kettering Cancer Center, grading systems and NARS([5ypN-3(kT-pT)+12]2/9,61) calculations. Their results were compared in terms of treatment outcomes.

The median follow-up time was 51 months (range 5-136). There was a significant relation between cT stage and the response in used grading systems(p < 0,001). Median overall(OS), local recurrence free(LRFS), and distant metastasis free(MFS) survival rates were 50, 48, and 45 months, respectively. 5-year OS, LRFS, and MFS rates were 71%, 92%, and 72%, respectively. According to the NARS and treatment response grating systems, a significant difference was found between the low risk and high risk groups in terms of OS, LRFS, and MFS rates. While it was not seen any difference in terms of OS and MFS, NARS was found to predict LRFS better than other grading systems. In multivariate analysis, high NARS was found to be correlated with worse OS and worse MFS. On the other hand, pCR was the another important factor affecting treatment outcomes.

While used systems except NARS group patients according to ypT status in surgical tissue, NARS add the value of ypN status in addition to ypT status. It could be suggested to use NARS to predict LRFS.

This study aimed to evaluate the predictive value of lymph node yield (LNY) for survival outcomes according to tumor response after preoperative chemoradiotherapy (PCRT) in patients with rectal cancer.

This study was a retrospective study conducted in a tertiary center. A total of 1,240 patients with clinical stage II or III rectal cancer who underwent curative resection after PCRT between 2007 and 2016 were included. Patients were categorized into the good response group (tumor regression grade [TRG], 0-1) or poor response group (TRG, 2-3). Propensity score matching was performed for age, sex, and pathologic stage between LNY of ≥12 and LNY of <12 within tumor response group. The primary outcome was 5-year disease-free survival (DFS) and overall survival (OS).

LNY and positive lymph nodes were inversely correlated with TRG. In good responders, 5-year DFS and 5-year OS of patients with LNY of <12 were better than those with LNY of ≥12, but there was no statistical significance. In poor responders, the LNY of <12 group had worse survival outcomes than the LNY of ≥12 group, but there was also no statistical significance. LNY of ≥12 was not associated with DFS and OS in multivariate analysis.

LNY of <12 showed contrasting outcomes between the good and poor responders in 5-year DFS and OS. LNY of 12 may not imply adequate oncologic surgery or proper staging in rectal cancer patients treated by PCRT. Furthermore, a decrease in LNY should be comprehended differently according to tumor response.

Chemotherapeutic agents are used to control tumor proliferation. However, their influence in the pre-metastatic niche of target organs has not been well studied. Oxaliplatin (OXA) is a drug applied in standard treatments of colorectal cancer (CRC), while the direct effect of which on the pre-metastatic microenvironment of the liver remains unclear.

Models of liver metastases were established with luciferase expressing CT26 cells in BALB/c and BALB/c-nude mice. Single-cell RNA Sequencing was performed to examine the immune microenvironment in the liver elicited by OXA. Immunofluorescence and flowcytometry were utilized to confirm the changes in the number of immune cells. LDH, CellTrace CFSE Cell Proliferation and apoptosis assays were conducted to explore the impact of OXA on T cells ex vivo. The correlation between chemotherapy-related lymphopenia and metastases was assessed by meta-analysis.

Herein we discovered that administration of OXA prior to the occurrence of liver metastasis actually accelerated tumor development and colonization in the liver. Single-cell RNA sequencing revealed that the landscape of the liver immune microenvironment had been changed to immunosuppressive phenotype. Macrophages after the treatment of OXA exhibited a high ability to inhibit the activation of T cells. Further investigation revealed a significant decrease in the number of T cells in the liver, particularly CD8+ T cells with reduced capacity of proliferation, activation, and killing. When mice were treated with T cell supplementation, the OXA-induced metastasis was notably abolished, indicating that the OXA-primed liver microenvironment could be reversed by the infusion of T cells. Consistent with our findings in mice, a meta-analysis was performed to verify that chemotherapy-related lymphopenia was associated with an inferior prognosis related with high incidence of metastasis, suggesting the pivotal role of chemotherapy in pre-metastatic niche formation. Furthermore, a notable reduction in the count of both macrophages and T cells was observed in the liver of colorectal cancer (CRC) patient undergoing OXA-based chemotherapy.

Our findings proposed that immunosuppressive microenvironment in liver induced by OXA enhanced liver metastasis of colorectal cancer, which highlighted a new consideration to balance the pro metastases and anti-cancer possibility of OXA treatment.

Advances in preoperative chemoradiotherapy and surgical techniques offered improvements in rates of locoregional recurrence but did not address distant metastasis. Traditionally, adjuvant chemotherapy has been administered with the goal of limiting systemic recurrences.

Evaluation of the efficacy and safety of adjuvant chemotherapy in patients with locally advanced rectal cancer after preoperative chemoradiotherapy and surgery.

From January 2017 to December 2018, 103 patients diagnosed with clinical stage II or III rectal cancer received adjuvant chemotherapy with capecitabine or XELOX regimens after neoadjuvant concurrent chemoradiotherapy and total mesorectal excision. Overall survival, disease-free survival, and toxicity were analyzed.

The median follow-up time was 52.5 months (6.5-66.8 months). The mean 3-year disease-free survival and 3-year overall survival were 86.2% (95% CI: 82.8-89.6) and 92.2% (95% CI: 86.9-97.5), respectively. The rate of hematologic and nonhematologic toxicity was low, mostly grades 1 and 2 including anemia, leucopenia, thrombocytopenia, and liver enzymes elevations were 85.4, 50.5, 42.8, and 45.6%, respectively.

The capecitabine and XELOX regimen in adjuvant settings for rectal cancer patients receiving neoadjuvant chemoradiotherapy and surgery was a safe and effective modality. Further randomized trials need to be conducted to evaluate the role of postoperative therapy for these individuals.

Neoadjuvant modified FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) chemotherapy with selective radiotherapy did not compromise pathologic complete response and tumor downstaging in locally advanced rectal cancer.

The study aimed to analyze disease-free survival and local recurrence of neoadjuvant chemotherapy with modified FOLFOXIRI (mFOLFOXIRI).

This was a prospective single-arm phase II study. A propensity score-adjusted method was implemented to compare outcomes against historical controls of chemoradiotherapy.

The study was conducted at single institutions.

One hundred 6 patients with stage II and III rectal cancers were included.

All patients received neoadjuvant mFOLFOXIRI chemotherapy before total mesorectal excision. Patients with mesorectal fascia-positive or ycT4a/b after reevaluation with MRI received radiation before surgery. Otherwise, immediate total mesorectal excision would be performed.

The primary end point was tumor downstaging (ypStage 0-I) rate, which was reported previously. Disease-free survival and local recurrence rate were the main outcomes for the current study.

After a median follow-up of 43.3 months, the 2-year disease-free survival rate was 85.6% and the 3-year disease-free survival rate was 78.9%. The local recurrence rate was 7.8% after surgery. After propensity score matching, 73 patients were available for comparison in each group. The pathologic complete response rate was 23.3% and 13.7% ( p = 0.14), the proportion of ypStage 0-I was 45.2% vs 39.7% ( p = 0.5), the 3-year disease-free survival was 87.6% vs 75.8% (HR = 0.46; 95% CI, 0.22-0.95, p = 0.037). The local recurrence rate in the mFOLFOXIRI group was 5.5% and in the chemoradiotherapy group was 4.1% ( p = 0.70). Patients receiving mFOLFOXIRI had a lower incidence of anastomotic fistula compared with the chemoradiotherapy group (5.5% vs 17.8%, p = 0.02).

This was a single-arm, nonrandomized phase II study.

Neoadjuvant mFOLFOXIRI with selective radiotherapy was feasible and safe, and it improved 3-year disease-free survival compared with propensity score-matched historical controls who received chemoradiotherapy. See Video Abstract at http://links.lww.com/DCR/B989 .Trial registration: NCT02217020.

ANTECEDENTES:La quimioterapia neoadyuvante con FOLFOXIRI modificado (ácido folínico, 5-fluoruracilo, oxaliplatino e irinotecan) con radioterapia selectiva no comprometió la respuesta patológica completa ni la reducción del estadio del tumor en el cáncer de recto localmente avanzado.OBJETIVO:El estudio tuvo como objetivo analizar la sobrevida libre de enfermedad y la recurrencia local de la quimioterapia neoadyuvante con FOLFOXIRI modificado (mFOLFOXIRI).DISEÑO:Este fue un estudio prospectivo de fase II de un solo brazo. Se implementó un método ajustado por puntaje de propensión para comparar los resultados con los controles históricos de quimiorradioterapia.ESCENARIO:El estudio se realizó en instituciones individuales.PACIENTES:Se incluyeron 106 pacientes con cáncer de recto en estadio II y III.INTERVENCIÓN:Todos los pacientes recibieron quimioterapia neoadyuvante con mFOLFOXIRI antes de la escisión total del mesorrecto. Los pacientes con fascia mesorrectal positiva o ycT4a/b después de la reevaluación con MRI recibirían radiación antes de la cirugía. En caso contrario, se realizaría una escisión mesorrectal total inmediata.PRINCIPALES RESULTADOS Y MEDIDAS:El criterio principal de valoración fue la tasa de disminución del estadio del tumor (ypEstadio 0-I), que se informó anteriormente. La sobrevida libre de enfermedad y la tasa de recurrencia local son los principales resultados del estudio actual.RESULTADOS:Después de una mediana de seguimiento de 43,3 meses, las tasas de sobrevida libre de enfermedad a 2 y 3 años fueron del 85,6 % y 78,9 %, respectivamente. La tasa de recidiva local fue del 7,8% tras la cirugía. Después del emparejamiento por puntaje de propensión, 73 pacientes estaban disponibles para la comparación en cada grupo. La tasa de respuesta patológica completa fue de 23,3 % y de 13,7 % (p = 0,14), la proporción de ypEstadio 0-I fue del 45,2 % frente al 39,7 % (p = 0,5), la SLE a los 3 años fue del 87,6 % frente al 75,8 % (HR = 0,46, IC del 95 % 0,22-0,95, p = 0,037) y la tasa de recurrencia local fue del 5,5 % y del 4,1 % (p = 0,70) en el grupo de mFOLFOXIRI frente al grupo de quimiorradioterapia, respectivamente. Los pacientes que recibieron mFOLFOXIRI tuvieron una menor incidencia de fístula anastomótica en comparación con el grupo de quimiorradioterapia (5,5 % frente a 17,8 %, p = 0,02).LIMITACIONES:Este fue un estudio de fase II no aleatorizado de un solo brazo.CONCLUSIONES:El mFOLFOXIRI neoadyuvante con radioterapia selectiva fue factible y seguro, y mejoró la SSE a los 3 años en comparación con los controles históricos emparejados por puntaje de propensión que recibieron quimiorradioterapia. Consulte Video Resumen en http://links.lww.com/DCR/B989 . (Traducción-Dr. Felipe Bellolio ).

The management of locally advanced rectal cancer (LARC) suffered changes thanks to the development of improved surgical procedures, radiation delivery, and chemotherapy. Although treatment options improved individually, the optimal order is still debated. Neoadjuvant chemo-radiotherapy followed by total mesorectal excision (TME) has been the "golden standard" for locally advanced rectal cancer. There is no common ground in international guidelines on the indications of adjuvant chemotherapy (ADJCHT), with differences between the American, European, and Japanese guidelines. This paper studies the preferences of Romanian oncologists in prescribing ADJCHT. We conducted a single-institution, retrospective study of all nonmetastatic, ECOG 0-1 LARC patients staged II-III who underwent TME and were admitted to the Oncology or Radiotherapy Department of Colțea Clinical Hospital, Bucharest between January 2017 and March 2021. A total of 186 patients were included in the study. A positive correlation was found between ADJCHT and each of the following: (y)pT > 2, (y)pN > 0, and the presence of perineural invasion (PNI+). A strong positive correlation was found between ADJCHT and the presence of at least one risk factor: (y)pT > 2, (y)pN > 0, PNI+, lymphovascular invasion, positive margins, or tumor grade > 1. Tumor downstaging decreased the risk of metastases in the first 2 years and was associated with the use of neoadjuvant radiotherapy, while adding neoadjuvant chemotherapy increased the chance of nodal downstaging. ADJCHT practice for LARC in Romania follows either NCCN or ESMO guidelines, at the discretion of the oncologist, due to the lack of national guideline.

In the current NCCN guidelines, the prognosis and adjuvant chemotherapy of patients who underwent neoadjuvant chemoradiotherapy (nCRT) are based on pre-radiotherapy clinical TNM (cTNM) stage. However, the value of neoadjuvant pathologic TNM (ypTNM) stage is not clearly described.

This retrospective study investigated the prognosis and adjuvant chemotherapy which based on ypTNM stage compared to cTNM stage. Between 2010 and 2015, a total of 316 rectal cancer patients who underwent nCRT, followed by total mesorectal excision (TME), were included for analysis.

Our findings revealed that cTNM stage was the only significant independent factor in the pCR group (HR = 6.917, 95% CI: 1.133-42.216, P = 0.038). In the non-pCR group, ypTNM stage was more important than cTNM stage in prognosis (HR = 2.704, 95% CI: 1.811-4.038, P < 0.001). In ypTNM III stage group, there was a statistically significant difference in prognosis between the patients with and without adjuvant chemotherapy (HR = 1.943, 95% CI: 1.015-3.722, P = 0.040), but there was no significant difference in cTNM III stage group (HR = 1.430, 95% CI: 0.728-2.806, P = 0.294).

We concluded that ypTNM stage, rather than cTNM stage, might be a more important factor in the prognosis and adjuvant chemotherapy of patients with rectal cancer who underwent nCRT.

Total neoadjuvant therapy (TNT) is a novel treatment strategy that is an alternative to preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). However, an optimal protocol for TNT has not yet been established. The present study will be an open-label, single-arm, single-center trial to develop a new protocol.

Thirty LARC patients at high risk of distant metastasis will receive CRT consisting of long-course radiation, concurrent with tegafur/uracil, oral leucovorin, irinotecan (TEGAFIRI), followed by mFOLFOX-6 or CAPOX before undergoing surgery.

Since previous findings showed a high percentage of grade 3-4 adverse events with the TEGAFIRI regimen for CRT and TNT, the primary outcome of this study will be safety and feasibility. Our regimen for CRT consists of the biweekly administration of irinotecan for good patient compliance. The novel combination approach of this treatment may improve the long-term outcomes of LARC.

Japan Registry of Clinical Trials jRCTs031210660.

There are few studies analyzing the cost of endoscopic resection and surgical resection in the treatment of submucosal colorectal cancer.

The objective was to perform a detailed cost analysis of endoscopic resection and surgical resection for submucosal colorectal cancer.

This was a retrospective observational study.

This study was conducted at a tertiary academic center.

Medical records of 484 patients with submucosal colorectal cancer who underwent endoscopic resection or surgical resection between July 2003 and July 2015 were reviewed.

The total costs during index admission and follow-up as well as clinical outcomes between the 2 groups were compared in the whole cohort and propensity score-matched cohort.

In the propensity score-matched analysis ( n = 155 in each group), the endoscopic resection and surgical resection groups did not show significant differences in the rates of procedure-related adverse events (6.5% vs 3.9%; p = 0.304) and recurrence (0.6% vs 1.3%; p > 0.99). Readmission was more common in the endoscopic resection group (40.6% vs 11.0%; p < 0.001) because 64 (41.3%) patients underwent additional surgery for endoscopic noncurative resection. The endoscopic resection group had a lower cost during the index admission (1335.6 vs 6698.4 USD; p < 0.001), whereas the surgical resection group had a lower cost during follow-up (2488.7 vs 5035.7 USD; p < 0.001). The total cumulative cost was lower in the endoscopic resection group (6371.3 vs 9187.1 USD; p < 0.001). The same trend was observed in the whole cohort without propensity score matching.

A limitation of this study was the retrospective nature of analysis.

The total cumulative cost for treatment and follow-up for submucosal colorectal cancer was lower in the endoscopic resection group, which had comparable oncologic outcomes as the surgical resection group. Endoscopic resection can be considered a cost-effective option for initial treatment for submucosal colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B881 .

ANTECEDENTES: Existen pocos estudios que analizan el costo de la resección endoscópica y la resección quirúrgica en el tratamiento del cáncer colorrectal submucoso.OBJETIVO: El objetivo fue realizar un análisis detallado de costos tanto de la resección endoscópica y la resección quirúrgica para el cáncer colorrectal submucoso.DISEÑO: Este fue un estudio observacional retrospectivo.AJUSTE: Este estudio se realizó en un centro académico terciario.PACIENTES: Se revisaron las historias clínicas de 484 pacientes con cáncer colorrectal submucoso que fueron sometidos a resección endoscópica o resección quirúrgica entre julio de 2003 y julio de 2015.PRINCIPALES MEDICIONES DE RESULTADOS: Los costos totales durante la admisión índice y el seguimiento, así como los resultados clínicos entre los dos grupos, fueron comparados en toda la cohorte y la cohorte emparejada por puntuación de propensión.RESULTADOS: En el análisis emparejado por puntuación de propensión ( n = 155 en cada grupo), los grupos de resección endoscópica y resección quirúrgica no mostraron diferencias significativas en las tasas de eventos adversos relacionados con el procedimiento (6,5% vs 3,9%, p = 0,304) y recurrencia (0,6% vs 1,3%, p > 0,99). La readmisión fue más común en el grupo de resección endoscópica (40,6% vs 11,0%, p < 0,001) porque 64 (41,3%) pacientes fueron sometidos a una cirugía adicional para lograr la resección en aquellos casos en que la resección endoscópica no fue curativa. El grupo de resección endoscópica tuvo un costo menor durante el ingreso índice (1335.6 vs 6698.4 USD, p < 0.001), mientras que el grupo de resección quirúrgica tuvo un costo menor durante el seguimiento (2488.7 vs 5035.7 USD, p < 0.001). El costo total acumulado fue menor en el grupo de resección endoscópica (6371,3 vs 9187,1 USD, p < 0,001). La misma tendencia se observó en toda la cohorte sin emparejamiento por puntuación de propensión.LIMITACIONES: La naturaleza retrospectiva del análisis.CONCLUSIONES: El costo total acumulado para el tratamiento y seguimiento del cáncer colorrectal submucoso fue menor en el grupo de resección endoscópica, que tuvo resultados oncológicos comparables a los del grupo de resección quirúrgica. La resección endoscópica puede considerarse una opción rentable para el tratamiento inicial del cáncer colorrectal submucoso. Consulte Video Resumen en http://links.lww.com/DCR/B881 . (Traducción-Dr Osvaldo Gauto ).

The therapeutic modalities for nonmetastatic rectal cancer are presently undergoing major changes. The standard treatment is multidisciplinary, combining radiotherapy, chemotherapy, and surgery. The aim of this minireview is to provide an update on the place of organ preservation in the treatment of nonmetastatic rectal cancer in 2022.

The multimodal strategy based on initial radiochemotherapy followed by radical surgery with excision of the mesorectum has improved oncological results but at the expense of morbidity and sequelae altering life quality. The strategy of rectal preservation has been proposed since the 2000s after the publication of the results of the Brazilian study that proposed a simple surveillance after radiochemotherapy without surgery in good responders. In fact, preoperative radiochemotherapy was able to obtain a complete histological response in 10 to 30% of case. In view of this non-negligible percentage of tumor sterilization, which may well increase with the standardization of total neoadjuvant treatment, a strategy of organ preservation can be proposed in these patients to avoid morbidity and postoperative sequelae.

This nonoperative approach is currently widely studied in certain patients who have a complete response (clinical, endoscopic, and radiological). However, the selection of these patients is not simple and still complex.

WD repeat domain 76 (WDR76) has been reported in multiple tumors, while without relation to chemotherapy resistance. 5-fluorouracil (5-FU) is widely adopted in treating colon cancer. However, the resistance of WDR76 and 5-FU in colon cancer remains unclear.

Limma package in R software was employed to analyze the differentially expressed genes. Western blot or quantitative real-time PCR (qRT-PCR) were run to assessed the gene expression. The cytotoxic effect was determined according to cell viability assay, colony formation assay in vitro. Cell apoptosis was assayed using flow cytometry. GSEA analysis was performed to identify pathways related to the target gene. Xenografted mice model was employed to evaluate the tumor growth.

Bioinformatic analysis revealed the higher expression of WDR76 in 5-FU sensitive colon cancer cells compared to resistant colon cancer cells, accompanied by the decreased mRNA expression of WDR76 in 5-FU resistant colon cancer cells. The overexpressed WDR76 resulted in the apoptosis and the downregulated colony numbers in 5-FU resistant colon cancer cells, leading to the elevated sensitivity of 5-FU. Meanwhile, knockdown of WDR76 enhances the resistance of 5-FU in colon cancer both in vitro and vivo, which was reversed by a specific inhibitor of HRAS, Kobe006. An important molecular mechanism of 5-FU resistance lies the degradation of HRAS induced by WDR76.

Our findings demonstrated a role of WDR76 as a promising target for reversing the resistance of colon cancer to 5-FU.

Early evaluation of the efficacy of first-line chemotherapy combined with bevacizumab in patients with colorectal cancer liver metastasis (CRLM) remains challenging. This study used 2-month post-chemotherapy spectral computed tomography (CT) to predict the overall survival (OS) and response of CRLM patients with bevacizumab-containing therapy.

This retrospective analysis was performed in 104 patients with pathologically confirmed CRLM between April 2017 and October 2021. Patients were treated with 5-fluorouracil, leucovorin, oxaliplatin or irinotecan with bevacizumab. Portal venous phase spectral CT was performed on the target liver lesion within 2 months of commencing chemotherapy to demonstrate the iodine concentration (IoD) of the target liver lesion. The patients were classified as responders (R +) or non-responders (R -) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at 6 months. Multivariate analysis was performed to determine the relationships of the spectral CT parameters, tumor markers, morphology of target lesions with OS and response. The differences in portal venous phase spectral CT parameters between the R + and R - groups were analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the predictive power of spectral CT parameters.

Of the 104 patients (mean age ± standard deviation: 57.73 years ± 12.56; 60 men) evaluated, 28 (26.9%) were classified as R + . Cox multivariate analysis identified the iodine concentration (hazard ratio [HR]: 1.238; 95% confidence interval [95% CI]: 1.089-1.408; P < 0.001), baseline tumor longest diameter (BLD) (HR: 1.022; 95% CI: 1.005-1.038, P = 0.010), higher baseline CEA (HR: 1.670; 95% CI: 1.016-2.745, P = 0.043), K-RAS mutation (HR: 2.027; 95% CI: 1.192-3.449; P = 0.009), and metachronous liver metastasis (HR: 1.877; 95% CI: 1.179-2.988; P = 0.008) as independent risk factors for patient OS. Logistic multivariate analysis identified the IoD (Odds Ratio [OR]: 2.243; 95% CI: 1.405-4.098; P = 0.002) and clinical N stage of the primary tumor (OR: 4.998; 95% CI: 1.210-25.345; P = 0.035) as independent predictor of R + . Using IoD cutoff values of 4.75 (100ug/cm³) the area under the ROC curve was 0.916, sensitivity and specificity were 80.3% and 96.4%, respectively.

Spectral CT IoD can predict the OS and response of patients with CRLM after 2 months of treatment with bevacizumab-containing therapy.

In this systematic review, the efficacy and safety of chronomodulated chemotherapy, defined as the delivery of chemotherapy timed according to the human circadian rhythm, were assessed and compared to continuous infusion chemotherapy for patients with advanced colorectal cancer. Electronic English-language studies published until October 2020 were searched. Randomised controlled trials (RCTs) comparing chronomodulated chemotherapy with non-chronomodulated (conventional) chemotherapy for the management of advanced colorectal cancer were included. The main outcomes were the objective response rate (ORR) and system-specific and overall toxicity related to chemotherapy. Electronic databases including Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Review were searched. In total, seven RCTs including 1,137 patients were analysed. Males represented 684 (60%) of the study population. The median age was 60.5 (range = 47.2-64) years. There was no significant difference between chronomodulated and conventional chemotherapy in ORR (risk ratio (RR) = 1.15; 95% confidence interval (CI) = 0.87-1.53). Similarly, there was no significant difference in gastrointestinal toxicity under the random effect model (RR = 1.02; 95% CI = 0.68-1.51). No significant difference was found regarding neurological and skin toxicities (RR = 0.64, 95% CI = 0.32-1.270 and RR = 2.11, 95% CI = 0.33-13.32, respectively). However, patients who received chronomodulated chemotherapy had less haematological toxicity (RR = 0.36, 95% CI = 0.27-0.48). In conclusion, there was no overall difference in ORR or haematologic toxicity between chronomodulated and non-chronomodulated chemotherapy used for patients with advanced colorectal cancer. Chronomodulated chemotherapy can be considered in patients at high risk of haematological toxicities.

Although extended lymph node dissection during colon cancer surgery is recommended in both Western and Eastern countries, the perception and clinical significance of main lymph node metastasis (MLNM) remains controversial.

In total, 1557 patients with colon cancer who underwent curative resection with D3 dissection were retrospectively analyzed. Clinicopathological factors associated with MLNM were analyzed. Kaplan-Meier survival analysis and log-rank tests were used to compare the prognosis between the MLNM and non-MLNM groups.

Multivariate analysis showed that overall survival (OS) [hazard ratio, 2.117 (0.939-4.774), p = 0.071] and recurrence-free survival (RFS) [hazard ratio, 2.183 (1.182-4.031), p = 0.013] were affected by the MLNM status independent of the TNM stage. Survival analysis demonstrated that among patients with stage III disease, the OS and RFS rates were significantly different between patients with and without MLNM (OS: p = 0.0147, RFS: p = 0.0001). However, the OS and RFS rates were not significantly different between patients who had stage III disease with MLNM and patients who had stage IV disease (OS: p = 0.5901, RFS: p = 0.9610).

MLNM is an independent prognostic factor for patients with colon cancer. The addition of the MLNM status to the current TNM classification may enhance the prognostic value of the TNM staging system and the clinical efficacy of adjuvant therapy in patients with colon cancer.

Neoadjuvant chemoradiation therapy (NCRT, 5-fluorouracil and radiation) followed by resection and adjuvant chemotherapy (AC) is one of the standard treatment paradigms for locally advanced rectal adenocarcinoma. However, the utility of AC in patients with pathologic lymph node (pLN)-negative disease is unclear. Our aim is to assess the value of AC stratified by pLN status.

The US Rectal Cancer Consortium database (2007-2017) was retrospectively reviewed for patients with clinical stage II and III rectal adenocarcinoma who received neoadjuvant chemoradiation (NACR) and curative-intent resection. Those who received neoadjuvant systemic chemotherapy or underwent local resection were excluded. Patients were categorized by pLN status. Primary outcome was overall survival (OS).

Of 213 patients, 70% had pLN-negative disease and 30% pLN-positive disease. Median age was 57 years, 65% were male, and median follow-up was 31 months. Among patients with pLN-negative disease, 74% received AC. Receipt of AC was not associated with improved 5-year OS (82% versus 74%, respectively; p = 0.16). This finding persisted on multivariable analysis. Of patients with pLN-positive disease, 83% received AC. Patients with pLN-positive disease demonstrated improved 5-year OS with receipt of AC (72% compared with 0% with no adjuvant chemotherapy, p = 0.04).

After receiving neoadjuvant chemoradiation, adjuvant chemotherapy for patients with pLN-negative disease does not appear to be associated with improved survival. Further validation and prospective studies are needed to evaluate the utility of adjuvant chemotherapy in this setting.

Rectal or anal canal adenocarcinoma with inguinal lymph node metastasis (ILNM) is rare and is associated with poor prognostic outcomes. This study aimed to elucidate the clinical significance of neoadjuvant therapy followed by selective inguinal lymph node dissection and total mesorectal excision for rectal or anal canal adenocarcinoma with clinically suspected ILNM.

This study enrolled 15 consecutive patients who underwent neoadjuvant therapy and curative resection for rectal or anal canal adenocarcinoma with clinically suspected ILNM between 2005 and 2019 at a single institution. Inguinal lymph node dissection was selectively performed on the side of suspected metastasis before neoadjuvant therapy. Short- and long-term outcomes were retrospectively reviewed.

Out of the15 patients, 11 were treated with neoadjuvant chemoradiation, three with chemotherapy, and one with chemoradiation followed by chemotherapy. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans were performed after neoadjuvant therapy in 14 patients. Five patients had negative FDG accumulation in inguinal lymph nodes on FDG-PET scan, and their inguinal lymph nodes were also pathologically negative for metastasis. Of the nine patients who had positive FDG accumulation, four had pathologically positive inguinal lymph nodes. Seven patients (46.7%) had inguinal seroma postoperatively. Five-year-overall survival was 77.5%, and 5-year-relapse-free survival was 64.2%. No patient had a recurrence in the inguinal region.

In patients with rectal or anal canal adenocarcinoma associated with clinical ILNM, radical resection with neoadjuvant therapy provides a good long-term survival.