Total neoadjuvant therapy(TNT) has improved complete pathologic response (pCR) rate and disease-free survival (DFS) in locally advanced rectal cancer (LARC), though an increased local recurrence rate (LRR) with short-course radiotherapy (SCRT) is concerning. Synergism between immunotherapy and radiotherapy may improve outcomes in LARC, even where microsatellite stable (MSS) tumours exist. The Averectal trial evaluated SCRT, followed by chemotherapy and immunotherapy with avelumab and total mesorectal excision (TME) in these patients.

Patients with LARC received SCRT (5 Gy x5 fractions), 6 cycles of mFOLFOX-6 plus avelumab every 2 weeks, followed by TME in an investigator-initiated, open-label, single-arm, multicentre, phase II study. The primary outcome was pCR vs. historical control. Secondary outcomes were 3-year DFS, local recurrence rate (LR) and the association of the ImmunoScore (IS) with outcomes including pCR, safety, and quality of life (QoL).

Out Of 44 MSS patients enrolled from 3 centres (July 2018 -October 2020), 40 completed treatment and analysed (65 % male, median age 58.5 [31.0, 74.0] years). Median follow-up was 44 months (11.4, 51.4). Fifteen patients (37.5 %) achieved pCR; and 67.5 % had a major pathologic response. Mean DFS was 42 months (37.9, 46.1). Mean OS was 46.3 months (44.4, 48.2). Median DFS and OS were not reached. Three-year DFS was 85 %. LRR was 2.5 %. Patients with vs. without pCR had higher mean IS (68 vs. 52, p = 0.036). Serious adverse events occurred in 23.5 % (one was related to avelumab). Three patients died (7.5 %), due to disease progression. QOL was similar between baseline and last follow-up.

Adding avelumab to neoadjuvant chemotherapy mFOLFOX6 after SCRT, followed by TME, improved pCR without increasing LRR, with acceptable toxicity and QOL.

The outcomes of neoadjuvant chemoradiotherapy (CRT) under non-smoking conditions in patients with locally advanced rectal cancer (LARC) remain unclear. The aim of the present study was to evaluate the outcomes in patients with LARC who underwent neoadjuvant CRT under non-smoking conditions, followed by total mesorectal excision (TME). To this end, the medical records of 28 patients treated with CRT and surgery for LARC between January 2014 and December 2019 were retrospectively analyzed. Smoking cessation was monitored by measuring carbon monoxide (CO) levels using a Smokerlyzer. Survival outcomes and clinicopathological factors associated with pathological complete response (pCR) were investigated. The median age was 66 (45-89) years, and 20 (71.4%) patients were male. A total of 16 (57.1%) patients were diagnosed with clinical stage III LARC. Seven patients smoked at diagnosis, with an average expiratory CO level of 8 (8-30) ppm. These patients ceased smoking and maintained exhaled CO levels <3 ppm before treatment. All patients successfully underwent CRT and TME. No major postoperative complications occurred. pCR was achieved in 8/28 patients (28.6%) and the 5-year recurrence-free and overall survival rates were 78.0% [95% confidence interval (CI), 57.4-89.5] and 85.7% (95% CI, 66.3-94.4), respectively. The median follow-up period was 60.1 (range, 5.6-114.6) months. Survival did not significantly differ between smokers and non-smokers at diagnosis. Clinically negative N stage (hazard ratio: 18.9; 95% CI, 1.63-218; P=0.0187) was significantly associated with pCR. In conclusion, neoadjuvant CRT under non-smoking conditions, as confirmed by measuring expiratory CO levels, followed by TME yields favorable pCR rates and survival outcomes in patients with LARC.

Total neoadjuvant therapy has been shown to increase pathological complete response and disease-free survival in patients with locally advanced rectal cancer after total mesorectal excision (TME). We hypothesised that total neoadjuvant therapy could maximise the number of patients attaining a clinical complete response who could then be instead referred to organ preservation with watch and wait.

This open-label, multicentre, single-arm, phase 2 study (CAO/ARO/AIO-16) was conducted at four centres across Germany. Patients aged 18 years or older with histologically confirmed cT1-2N1-2 or cT3a-dN0/N1-2 rectal adenocarcinoma up to 12 cm from the anal verge and without distant metastases received chemoradiotherapy. Radiotherapy was administered in daily fractions of 1·8 Gy, 5 days per week, starting at day 1 and ending at day 38, for a total of 28 fractions and total dose of 50·4 Gy. Concomitant fluorouracil (250 mg/m2 per day as a continuous venous infusion from day 1 to day 14 and day 22 to day 35) and oxaliplatin (50 mg/m2 intravenously on days 1, 8, 22, and 29) were administered. Chemoradiotherapy was followed by three cycles of consolidation FOLFOX (fluorouracil [2400 mg/m2 over 46 h by continuous venous infusion], oxaliplatin [100 mg/m2 intravenously as a 2-h infusion], and leucovorin [400 mg/m2 intravenously as a 2-h infusion]) starting on days 57, 71, and 85. Response assessment was scheduled on day 106 after the start of total neoadjuvant therapy and included digital rectal examination, rectoscopy, and pelvic MRI. In case of a clinical complete response, patients were scheduled for a watch and wait surveillance protocol. Patients with a near clinical complete response on day 106 were offered a second assessment on day 196. In case of conversion to a clinical complete response on this repeated assessment, the same watch and wait surveillance protocol was initiated. Alternatively, local excision was considered on day 196 if technically feasible. In all other cases, immediate TME surgery was recommended. The primary endpoint was the clinical complete response rate on day 106 or 196 assessed in patients who started chemoradiotherapy (intention-to-treat population). Toxicity was also assessed in this patient population. The study was registered with ClinicalTrials.gov (NCT03561142) and is complete.

Between June 1, 2018, and Oct 7, 2020, we enrolled 93 patients, of whom 91 (mean age 61 years [SD 10]; 61 [67%] men and 30 [33%] women) started chemoradiotherapy, 88 started consolidation chemotherapy, and 88 had a response assessment on day 106. At this first assessment, 13 (15%) patients were classified as having a clinical complete response and were assigned to watch and wait, 33 (38%) met criteria for a near clinical complete response and were scheduled for reassessment, and 42 (48%) had a poor response and were referred for immediate TME. At the second assessment, on day 196, 21 (64%) of 33 patients converted to a clinical complete response, two underwent local excision with a pathological complete response (and were also assigned to watch and wait), and ten had TME. Therefore, for the primary endpoint, 34 (37%) of the initial 91 patients attained a clinical complete response after total neoadjuvant therapy. Overall, 33 (36%) of 91 patients developed grade 3 or 4 toxicity during total neoadjuvant therapy. 17 (19%) patients developed grade 3 toxicity during chemoradiotherapy, with no grade 4-5 toxicity occurring at this treatment stage. The most frequently reported grade 3 toxicities during chemoradiotherapy were diarrhoea in nine (10%) patients and infections in six (7%). During consolidation chemotherapy, 17 (19%) of 88 patients had grade 3 toxicities, the most common of which were leucopenia (in seven [8%] patients) and neutropenia (in seven [8%]). One (1%) patient had grade 4 neutropenia and one patient died of COVID-19-associated pneumonia. Grade 3 and grade 4 adverse events during follow-up were recorded in 19 (21%) of 91 patients.

Upfront chemoradiotherapy and three cycles of consolidation FOLFOX result in a high rate of clinical complete response with an acceptable toxicity profile. Total neoadjuvant therapy combined with a watch and wait approach after a clinical complete response can be considered for patients with locally advanced rectal cancer seeking an alternative to TME surgery.

Medical Faculty Tübingen.

As patients with rectal cancer with clinical complete response (cCR) after neoadjuvant therapy may be safely spared Total Mesorectal Excision (TME), strategies to maximize cCR are needed.

We conducted a single-arm phase II study to determine whether dose-escalated short-course radiotherapy (25 Gy/5 fractions + 5 Gy/1 fraction boost) followed by eight cycles of FOLFOXIRI increased cCR rates among adult patients with > T2N0M0 or low T2N0 rectal cancer.

Between 2020 and 2023, we enrolled 37 patients, of whom 27 (73 %) had at least one high-risk feature (cT4, extramural vascular invasion [EMVI], N2, threatened circumferential resection margin, positive lateral node). At primary endpoint assessment, nine (24 %) patients had cCR on both endoscopy and MRI, and pursued organ preservation (OP). Fourteen (38 %) patients had cCR only on endoscopy, nine of whom pursued OP. Of the 18 patients who pursued OP, nine had local regrowth at two years from radiotherapy start, with two-year TME-free survival of 26 %. Baseline factors significantly associated with not achieving OP included age < 50 years and T4 disease. At mid-treatment restaging, patients who achieved OP were significantly less likely to have persistent node positivity, EMVI, and endoscopically visible tumor. Grade 3+ adverse events at least possibly attributed to chemotherapy and radiotherapy occured in 51% and 43% of patients, respectively.

Short-course radiotherapy with a boost followed by FOLFIXIRI results in OP in one-quarter of patients with high-risk rectal cancer, with poorer response among younger patients and T4 disease. Mid-treatment response may help guide timely decision-making regarding treatment.

Rectal MRI studies used to stage and guide surgical or nonsurgical management of rectal cancer may harbor incidental findings (IFs) of varying significance. St George's Hospital uses a four-sequence MRI protocol which does not employ diffusion-weighted imaging (DW-MRI).

To determine the frequency and significance of incidental findings identified when using a rectal MRI protocol which does not employ DW-MRI.

Retrospective analysis of rectal MRI study reports for IFs and stratifying their significance. Medical records were reviewed to clarify IFs of interest.

One hundred thirty-four studies met the inclusion criteria for the study (75 men, mean age 65). 51/134 (38%) of studies had IFs. Fifteen percent (n = 7/46) of baseline studies for a new cancer had significant IFs. The commonest IF was diverticular disease (n = 10); however, a bladder malignancy was also identified.

Clinically significant IFs exist in 12% of patients undergoing rectal MRI, and any type of IFs exist in 38% of patients undergoing rectal MRI studies. The rate of significant IFs is comparable with other authors both in rectal and prostate MRI but with fewer overall IFs, possibly due to the lack of DW-MRI sequences in our local protocol. Our study is the first to assess IFs using a rectal MRI protocol which does not employ DW-MRI, and the results should be considered by centers when planning their rectal MRI protocol.

This study investigates the functional outcomes of patients with low rectal cancer undergoing inter-sphincteric resection (ISR) following brachytherapy boost radiotherapy (BoRT), compared to those who underwent ISR after standard chemoradiotherapy. BoRT is an alternative to total neoadjuvant therapy for increasing organ preservation rates in low rectal cancers. However, its impact on sphincter function following stoma reversal remains unclear.

The study involved a retrospective analysis of 145 patients treated at a single institution between 2013 and 2021. Eighteen patients received pre-operative BoRT and were compared with 127 patients who did not, using propensity score matching based on age, sex, body mass index, and tumor distance from the anal verge with match ratio 1:4. Functional outcomes were assessed six months post-stoma reversal using the Low Anterior Resection Syndrome (LARS) Score, Wexner Score, and Kirwan Grade.

The results revealed that patients in the boost RT group had significantly worse functional outcomes, with a median LARS score of 36 (very high) compared to 10 in the no boost group (p < 0.001). Similarly, the median Wexner score was higher in the boost RT group (17 vs. 8, p < 0.001). The Kirwan Grade was consistent across both groups.

This study highlights the detrimental impact of BoRT on functional status, underscoring the importance of comprehensive patient counselling before initiating BoRT in candidates eligible for sphincter preservation. If optimal outcomes are not achieved following brachytherapy boost, surgical options like ISR or APR should be thoroughly discussed with patients to ensure informed decision-making.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effectiveness and safety of total neoadjuvant therapy versus standard therapy in individuals with locally advanced rectal cancer.

Preoperative chemoradiotherapy (CRT) is administered for locally advanced rectal cancer (LARC); however, its efficacy and toxicity vary among patients. This study aimed to elucidate the relationship between the gut microbiota and the effectiveness and adverse events of CRT.

This prospective study included 21 patients with LARC with no history of antibiotic or probiotic administration for 6 months. Tumour mucosa, non-tumour mucosa and faecal samples were collected before and after CRT, and bacterial DNA was extracted. Metataxonomic analysis targeting the V3 and V4 regions of the 16S rRNA gene was conducted to determine the diversity and composition of the microbiota. Linear discriminant analysis effect size (LEfSe) was used to explore potential bacterial taxa predicting pathological complete response (pCR) and treatment-associated diarrhoea, which are major adverse events of CRT.

Among the 21 patients, five achieved pCR and seven experienced severe treatment-associated diarrhoea. There were no significant differences in α-diversity and β-diversity of the microbiota between the groups at any sampling sites before or after CRT. Exploratory analysis using LEfSe identified Peptostreptococcus, Coprococcus and Phoceaicola in the tumour mucosa before CRT as significant indicators for achieving pCR. Additionally, Collinsella, Haemophilus and Desulfovibrionaceae are associated with treatment-associated diarrhoea. Microbiome composition changed before and after CRT, with a notable decrease in the genus Fusobacterium_C and other taxa. β-diversity in the tumour area also changed significantly (P = 0.03).

This study suggests an association between the gut microbiota, the therapeutic effectiveness of CRT and the occurrence of treatment-associated diarrhoea in rectal cancer. These results indicate the potential for predicting treatment efficacy and adverse events based on the microbiota composition.

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.

Neoadjuvant radiochemotherapy (NARCT) is an established standard of care in various tumor entities, promoting high response rates at commonly lower toxicities as compared to adjuvant approaches. This retrospective analysis was designed to investigate NARCT in early-stage high-risk cervical cancer.

Forty patients with early-stage high-risk cervical cancer (i.e., L1, V1, G3, N+, > 2/3 stromal invasion, > 4 cm tumor size, borderline resectability) were treated with NARCT prior to surgical resection. Downstagings based on clinical, imaging, and pathological responses were recorded. Survival rates were calculated according to Kaplan-Meier, and prognostic factors were analyzed with uni- and multivariable Cox regression analyses using SPSS software (v. 26; IBM Corp., Armonk, NY, USA).

Both NARCT and subsequent tumor resection were feasible and conducted in 39 of 40 patients (95%). Early toxicity was moderate, with no grade 3 or higher toxicities following NARCT and surgery. NARCT yielded significant downstaging in all patients, and pathological complete remission (pCR) was achieved in 14 patients (36%). After 5 years, overall survival (OS), freedom from local progression (FFLP), and freedom from distant progression (FFDP) rates were 84.2%, 75.9%, and 73.1%, respectively. Late proctitis (grade 1 in 8%) and urinary cystitis (grade 1-3 in 35%) occurred at acceptable rates.

In resectable early-stage high-risk cervical cancer, NARCT is feasible and safe. Clinical, imaging, and pathological response rates are high. Impressive long-term survival and tumor control rates at modest toxicities encourage the initiation of a prospective and randomized trial.

The primary objective of this study was to determine the clinical impact of using sigmoid take-off (STO) in the management of rectal cancer. We also evaluated the inter-observer reliability in the identification of STO.

This retrospective study reviewed staging MRI of patients with mid and high-rectal cancers performed between January 2019 and December 2022. The location of the tumour was reclassified based on STO as defined by D'Souza et al. (2018) and compared with the location determined based on distance from the anal verge. The proportions of cases that show a change in tumour location from rectal cancer to sigmoid cancer and the potential change in treatment were noted. The interobserver agreement for the location of STO and the location of tumours from STO was studied among four subspecialised abdominal radiologists.

Out of 134 rectal cancer patients included, STO-based assessment resulted in the reclassification of 13.4% (n=18) cases into sigmoid cancer. There was, however, no change in the stage of cancer. Among these 18 patients, there would have been a change in management in 5 patients had the initial assessment been a sigmoid cancer. There was excellent agreement among the radiologists for measuring the distance of STO from the anal verge (ICC = 0.883, p<0.001) and determining the location of the tumour based on STO (K = 0.82, p<0.001).

Using STO changed the location of tumours in 13.4% of high- and mid-rectal cancers. There was excellent agreement among radiologists regarding determining STO and identifying tumour locations using STO.

Guidelines for resectable locally advanced rectal cancer (LARC) advocate for neoadjuvant radiotherapy (NRT) followed by surgery as the standard approach. However, recent trials have reported no oncological benefits of NRT-based therapy for middle or lower rectal cancer, raising the question of whether NRT followed by surgery remains the optimal treatment approach for resectable LARC overall.

To compare the outcomes of NRT followed by surgery vs up-front surgery for resectable LARC.

This cohort study, using a target trial emulation framework with nationwide registries in Taiwan, included patients undergoing curative resection for resectable LARC (cT1-2N1-2, cT3Nany) between January 1, 2014, and December 31, 2017, with follow-up until December 31, 2020. Data were analyzed from January 1, 2024, to February 15, 2025.

NRT.

The primary outcomes were overall survival (OS) and local recurrence (LR). The secondary outcome was intraoperative diverting stoma outcomes.

A total of 4099 patients were analyzed, including 1436 patients undergoing NRT followed by surgery (median [IQR] age, 62.0 [53.0-71.0] years; 1036 [72.1%] male) and 2663 patients undergoing up-front surgery (median [IQR] age, 65.0 [56.0-74.0] years; 1626 [61.1%] male). NRT followed by surgery, compared with up-front surgery, was associated with higher 3-year OS rates (88.5% vs 85.2%; hazard ratio [HR], 0.74; 95% CI, 0.59-0.92) but higher permanent diverting stoma rates (20.6% vs 11.1%; relative risk [RR], 1.91; 95% CI, 1.62-2.25); LR rates were not significantly different (5.7% vs 6.6%; HR, 0.78; 95% CI, 0.55-1.11). Subgroup analysis revealed that compared with up-front surgery, NRT followed by surgery was associated with improved outcomes in middle or lower rectal cancer but not upper rectal cancer (OS: HR, 1.54; 95% CI, 0.82-2.90; LR: HR, 1.08; 95% CI, 0.23-5.00). NRT followed by surgery was associated with significantly increased risks of permanent diverting stomas across different tumor heights, particularly in upper rectal cancer (RR, 3.54; 95% CI, 1.44-8.69).

In this cohort study of nationwide registries in Taiwan, NRT followed by surgery was associated with improved oncological outcomes for overall resectable LARC, with excessive diverting stoma nonreversal as the trade-off. However, the benefits of NRT were not observed for upper rectal cancer. These findings raise concerns about potential harm from NRT and advise caution when performing NRT for upper rectal cancer.

Predicting response to neoadjuvant therapy in locally advanced rectal cancer (LARC) is challenging. Organ preservation strategies can be offered to patients with complete clinical response. We aim to evaluate MRI-derived radiomics models in predicting complete pathological response (pCR).

Search included MEDLINE, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews (CDSR) for studies published before 1st February 2024. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and Radiomics Quality Score (RQS) tools were used to assess quality of included study. The research protocol was registered in PROSPERO (CRD42024512865). We calculated pooled area under the receiver operating characteristic curve (AUC) using a random-effects model. To compare AUC between subgroups the Hanley & McNeil test was performed.

Forty-four eligible studies (12,714 patients) were identified for inclusion in the systematic review. We selected thirty-five studies including 10,543 patients for meta-analysis. The pooled AUC for MRI radiomics predicted pCR in LARC was 0.87 (95% CI 0.84-0.89). In the subgroup analysis 3 T MRI field intensity had higher pooled AUC 0.9 (95% CI 0.87-0.94) than 1.5 T pooled AUC 0.82 (95% CI 0.80-0.83) p < 0.001. Asian ethnicity had higher pooled AUC 0.9 (95% CI 0.87-0.93) than non-Asian pooled AUC 0.8 (95% CI 0.75-0.84) p < 0.001.

We have demonstrated that 3 T MRI field intensity provides a superior predictive performance. The role of ethnicity on radiomics features needs to be explored in future studies. Further research in the field of MRI radiomics is important as accurate prediction for pCR can lead to organ preservation strategy in LARC.

To examine the clinical impact of transanal total mesorectal excision (TaTME) for locally advanced rectal cancer after neoadjuvant chemoradiotherapy (NACRT).

This retrospective study included 91 patients undergoing surgery for rectal cancer after NACRT between 2011 and 2022. Among them, 24, 22, and 45 patients underwent open (Open), conventional laparoscopic (Lap), and TaTME surgeries, respectively. We compared their clinical outcomes.

Operative time, blood loss, transfusion, morbidity, and hospital stay were significantly lower in the TaTME group than in the Open or Lap groups. The multivariate regression analyses identified only the TaTME approach as a significant factor for reducing morbidity. Both 3 yrear relapse-free survival (RFS) and local recurrence-free survival (LRFS) were significantly better in the TaTME group than in the Open or Lap groups (3 yr RFS: 94.7%, 80.4%, and 66.7%, and 3 yr LRFS: 100%, 90.5%, and 82.2% for the TaTME, Lap, and Open groups, respectively). Multivariate analyses of potential risk factors for recurrence identified body mass index, combined resection, and pathological stage, but not the TaTME approach, as significant predictors of recurrence.

TaTME reduced morbidity significantly in patients with locally advanced rectal cancer undergoing NACRT, compared with open or laparoscopic surgery.

This network meta-analysis examined the efficacy of different types of neoadjuvant therapy (NAT) for rectal cancer in improving clinical and pathologic outcomes.

PRISMA-compliant systematic review of PubMed and Scopus including only randomized clinical trials comparing two or more NAT regimens for rectal cancer. A network meta-analysis was undertaken for the main outcomes, including pathological complete response (pCR), disease downstaging, R0 resection, permanent stoma, and major adverse effects. Risk of bias was assessed using the ROB-2 tool.

19 randomized controlled trials incorporating 7037 patients (62 % males) were included in the analysis. Compared to standard neoadjuvant chemoradiation (NCRT), consolidation total neoadjuvant therapy (TNT) (OR: 1.82, 95 % CI: 1.46-2.27; p < 0.001) and induction TNT (OR: 1.72, 95 % CI: 1.31-2.26; p < 0.001) had higher odds of achieving pCR. Induction TNT was also significantly associated with higher odds of major adverse effects than was NCRT (OR: 3.14, 95 % CI: 2.50-3.94; p < 0.0001). Compared to NCRT, long course chemotherapy significantly increased the odds of R0 resection (OR: 1.42, 95 % CI: 1.13-1.78; p = 0.002), while consolidation TNT significantly increased organ preservation rates (OR: 2.82, 95 % CI: 1.58-5.05; p < 0.001). Short course radiotherapy doubled the odds of positive circumferential resection margins (CRM) compared to NCRT (OR: 1.99, 95 % CI: 1.11-3.55; p = 0.02).

Consolidation and induction TNT were superior in achieving better pathological outcomes in rectal cancer, offering significant benefits over standard NCRT. However, they were associated with a higher risk of adverse effects. Conversely, short course radiotherapy was linked to higher rates of positive CRM.

Flavonoids are a group of polyphenolic compounds distributed in vegetables, fruits and other plants, which have considerable antioxidant, anti‑tumor and anti‑inflammatory activities. Several types of gastrointestinal (GI) cancer are the most common malignant tumors in the world. A large number of studies have shown that flavonoids have inhibitory effects on cancer, and they are recognized as a class of potential anti‑tumor drugs. Therefore, the present review investigated the molecular mechanisms of flavonoids in the treatment of different types of GI cancer and summarized the drug delivery systems commonly used to improve their bioavailability. First, the classification of flavonoids and the therapeutic effects of various flavonoids on human diseases were briefly introduced. Then, to clarify the mechanism of action of flavonoids on different types of GI cancer in the human body, the metabolic process of flavonoids in the human body and the associated signaling pathways causing five common types of GI cancer were discussed, as well as the corresponding therapeutic targets of flavonoids. Finally, in clinical settings, flavonoids have poor water solubility, low permeability and inferior stability, which lead to low absorption efficiency in vivo. Therefore, the three most widely used drug delivery systems were summarized. Suggestions for improving the bioavailability of flavonoids and the focus of the next stage of research were also put forward.

To determine a population-based comparative matched overall survival analysis for patients undergoing curative resection for sigmoid, rectosigmoid, and rectal cancers stage by stage.

Patients who underwent curative surgery for nonmetastatic adenocarcinoma of the sigmoid, rectosigmoid, and rectum between 2000 and 2020 were identified using the US SEER cancer registry data. Each anatomical subsegment was matched in a 1:1 ratio based on age, sex, time of surgery, grade of differentiation, and histopathological stage. Multivariate (MV) Cox regression analysis was conducted.

A total of 19,607 patients fulfilled the criteria per group. Whereas chemotherapy rates were comparable among groups, radiotherapy rates were significantly higher in the rectum. Compared to the initial time period (2000-2005), there was a significant improvement in 3- and 5-year overall survival rates for each stage in the time period of 2016-2020. During the study period, a 10% improvement was observed for Stage-2 and Stage-3 patients for each site (p < 0.05). MV analysis showed that sex (p < 0.001), primary cancer site (p < 0.001), year category (p < 0.001), age (p < 0.001), stage (p < 0.001), degree of differentiation (p < 0.001), and CTx status (p < 0.001) were independently associated with overall survival.

This large population-based, comprehensive registry study demonstrates significant survival differences among sigmoid, rectosigmoid, and rectal cancers. Further studies defining distinct landmarks between rectal and colon cancers may improve treatment approaches, cancer care, and survival.

To investigate the value of pretreatment magnetic resonance imaging (MRI) features in predicting a complete response to total neoadjuvant treatment (TNT) in locally advanced rectal cancer (LARC).

The data of patients who received TNT were analyzed retrospectively. MRI features, including T stage, morphology, length, and volume; the presence of MR-detected extramural venous invasion (mrEMVI), the number of mrEMVI, and the diameter of the largest invaded vein; main vein mrEMVI; presence of MR-detected tumor deposits (mrTDs), the number of mrTDs, and the size of the largest mrTD; MR-detected lymph node status (mrLN); tumor distance from the anal verge; mesorectal fascia involvement (mrMRF + ); and mean apparent diffusion coefficient (ADC) values were recorded. Patients were classified as complete (CRs) or noncomplete responders (non-CRs) according to the pathological/clinical outcomes. For patients managed nonoperatively, a sustained clinical complete response for > 2 years was deemed a surrogate endpoint for complete response. The MRI parameters were categorized into three distinct groups: baseline, advanced, and quantitative features, and were analyzed using multivariable stepwise logistic regression. The ability to predict complete response was evaluated by comparing different combinations of MRI parameters, and performance on an "independent" dataset was estimated using bootstrapped leave-one-out cross-validation (LOOCV).

The data of 84 patients were evaluated (CRs, n = 44; non-CRs, n = 40). The optimal model, which included baseline and quantitative MRI features, achieved an area under the curve of 0.837 for predicting complete response. Selected predictors were T stage and ADC mean value. Advanced MRI features did not improve the performance of the model.

A multivariable model combining T stage and the ADC mean value can help identify LARC patients who are likely to a achieve complete response before the initiation of TNT.

Carcinoma rectum is a major health issue in India as well as the rest of the world. Cases of rectal cancers are often diagnosed late because of mimicking symptoms with haemorrhoids/fissures and lack of awareness. In this study, we analysed the clinico-demographic profile of patients with carcinoma rectum, attending a tertiary care centre of Eastern India over the last 2 years. We analysed the database of radiotherapy OPD of a tertiary care centre of Eastern India, and collected the demographic, clinical and treatment data of rectal carcinoma patients who attended our OPD between 2021 and 2023. The objective was to assess the demographic and clinical profile of these patients and compare with those reported from other parts of the India as well as rest of the world. Data of total 76 patients were analysed in this study. The mean age of the study population was 50.7 (± 13.59) years. A striking 40% of patients were below 50 years of age. Stage III was the most common (43%) TNM stage at presentation. 15.7% presented with metastatic disease with the liver being the most common site of metastasis. 15.7% of patients underwent upfront surgery either as trans-anal resection or trans-abdominal resection of tumour. Most of the patients (56.5%) had gone through surgery after neo-adjuvant therapy (either total neo-adjuvant therapy or neo-adjuvant radiotherapy). Around 64.4% (n = 49) of patients received radiation as part of total neo-adjuvant therapy (TNT). Eight (10.5%) patients received adjuvant therapy after definitive surgery. To conclude, it can be said that this study revealed involvement of younger population, emergence of poor prognostic histologies and presence of disease at an advanced stage, all of which should be counted as warning signs for the picture rectal carcinoma of India. More researches are required in this field for detection of risk factors, prevention and treatment.

Pelvic exenterations (PEs) are technically demanding procedures performed with curative intent for advanced malignancies to improve patient survival while balancing morbidity and functional outcomes. The majority of United States (US) data regarding PE for rectal cancers originate from single-center series.

We aimed to investigate patterns of care and oncologic outcomes for primary rectal cancer patients undergoing PE in a national registry.

The National Cancer Database (2004-2019) was queried for adults with a pT4 rectal adenocarcinoma. Logistic regression identified factors associated with positive margins. Multivariable Cox regression estimated treatment effects on overall survival (OS).

Of 673 patients (73% <65 years of age, 39% male, 82% White), median follow-up was 39 months. The majority received neoadjuvant chemotherapy (76%) and radiation (75%), while adjuvant chemotherapy (37%) and radiation (13%) were less common. Twenty-four percent had positive margins (R1 = 98, R2 = 11, R + NOS = 48). Univariable analysis demonstrated that only nodal involvement was associated with higher positive margin rates (odds ratio 1.75, 95% confidence interval [CI] 1.22-2.51). Five-year OS for R0 and R+ resections were 55% and 33%, respectively. On multivariable analysis, age <65 years (hazard ratio [HR] 0.73, 95% CI 0.53-0.99) and adjuvant chemotherapy (HR 0.62, 95% CI 0.47-0.82) were associated with improved OS, while N+ status (HR 2.13, 95% CI 1.67-2.70) and positive margins (HR 1.82, 95% CI 1.41-2.35) portended worse prognosis. No significant associations were observed between outcomes and institutional volume.

One in four US patients undergoing PE for locally advanced rectal cancer had an R+ resection regardless of center volume. Quality of surgical resection to achieve negative margins remains the most relevant prognostic factor.

Over the past few decades, considerable progress has been made in the treatment of rectal cancer, leading to a reduction in local recurrence rates and an improvement in prognosis. The current German S3 guideline on colorectal cancer recommends neoadjuvant therapy for UICC stage II and III tumours of the middle and lower rectum. Primary surgery is still recommended for UICC I tumours, although exceptions are being discussed for certain subgroups, such as cT1/2 tumours with questionable nodal involvement. Current trials are focusing on multimodality treatment concepts, in particular total neoadjuvant therapy (TNT), which has been examined in several phase II and phase III trials. Therapies with selective omission of neoadjuvant radiotherapy and organ-preserving approaches are also being investigated. This review provides a comprehensive overview of the current evidence on neoadjuvant treatment of rectal cancer, highlights new multimodal treatment approaches, and discusses future challenges and opportunities to optimise treatment according to stage and to provide patients with the best possible individualised treatment.

Local resection (LR) in rectal cancer is indicated in stage T1N0M0 without unfavorable pathological factors, achieving oncologically satisfactory outcomes through transanal endoscopic surgery techniques. However, the initial step involves accurate staging and selection of these tumors through specific tests conducted in specialized colorectal units. For T2N0M0 tumors and T1 tumors with poor prognostic factors, the standard treatment is total mesorectal excision (TME), a procedure associated with high postoperative morbidity and mortality, functional impairments, and reduced quality of life. Therefore, new organ-preservation strategies are being explored as alternatives to TME. These include neoadjuvant therapy combined with LR, which has shown promising results, and neoadjuvant therapy followed by a "Watch and Wait" approach -where patients with complete clinical response are selected for strict surveillance- as an ideal future treatment, although there are still current challenges to be addressed.

Background/Objectives: The management of locally advanced rectal cancer has evolved significantly, shaped by advances in multimodal neoadjuvant therapy and a growing emphasis on organ preservation through the watch-and-wait approach. These advancements, however, introduce complex treatment decisions that require careful consideration by both patients and clinicians. Methods: This narrative review explores the evolution of the management of locally advanced rectal cancer and the role of shared decision-making in guiding treatment decisions, particularly for patients facing decisions between surgical resection and watch-and-wait. Additionally, it discusses the development of tools to aid in shared-decision making, current challenges in implementing shared decision-making and future directions for improvement patient centered care in locally advanced rectal cancer management. Results: Considerations for decision making include anatomical considerations that influence surgical options, the potential benefits and risks of watch-and-wait versus surgical resection of the rectum, and the impact of treatment on bowel, urinary, and sexual function. Additionally, patients must weigh the long-term implications of their choices on quality of life. Conclusions: Shared decision-making has emerged as a critical component of patient-centered care and ensures that treatment decisions align with patients' values and priorities. Given the preference-sensitive nature of the management of locally advanced rectal cancer, shared decision-making plays an important role in helping patients navigate these decisions.

The controversy surrounding the continuation of postoperative adjuvant chemotherapy (AC) for locally advanced rectal cancer patients who underwent neoadjuvant therapy (NAT) still existed. The study aimed to identify the individuals that would benefit from AC from those with stage ypII/III rectal cancer. Data for this retrospective study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and the local database. Subgroup differentiation of the beneficiary population by classification and regression tree analysis. The primary endpoint was overall survival (OS). 15,671 patients were included from the SEER database and 508 patients from local database. The proportions receiving AC were 41.9% in the SEER database and 77.6% in local database, respectively. Analysis results illustrated that the AC benefited population in the SEER database was characterized as: stage ypT4/N + patients (HR 0.75, 95% CI 0.69-0.82, p < 0.001); stage ypT3N0 patients aged 70 years or older (HR 0.69, 95% CI 0.56-0.83, p < 0.001). Moreover, stage ypT4/N + patients also significantly benefited from AC in local database (HR 0.48, 95% CI 0.31-0.74, p < 0.001). The analysis of the two databases showed that stage ypT3N0 patients aged < 70 years could not significantly benefit from AC (HR 0.90, p = 0.114 in the SEER database; HR 0.90, p = 0.960 in local database). Postoperative adjuvant chemotherapy provides a significant benefit in patients with stage ypT4/N + rectal cancer following neoadjuvant therapy. Our study discovered that locally advanced rectal cancer patients with aggressive tumors might benefit from postoperative adjuvant chemotherapy and prolonged the survival.

Statins have been shown to improve the possibility of a pathological complete response (pCR) in patients with locally advanced rectal cancer when given in combination with neo-adjuvant chemo-radiation (NACTRT) in observational studies. The primary objective of this phase II randomized controlled trial (RCT) is to determine the impact of rosuvastatin in improving pCR rates in patients with locally advanced rectal cancer who are undergoing NACTRT. The secondary objectives are to compare adverse events, postoperative morbidity and mortality, disease-free survival (DFS), and overall survival in the two arms and to identify potential prognostic and predictive factors determining outcomes. If the study is positive, we plan to proceed to a phase III RCT with 3-year DFS as the primary endpoint.

This is a prospective, randomized, open-label phase II/III study. The phase II study has a sample size of 316 patients (158 in each arm) to be accrued over 3 years to have 288 evaluable patients. The standard arm will receive NACTRT while the intervention group will receive 20 mg rosuvastatin orally once daily along with NACTRT for 6 weeks followed by rosuvastatin alone for 6-10 weeks until surgery. All patients will be reviewed after repeat imaging by a multidisciplinary tumor board at 12-16 weeks after starting NACTRT and operable patients will be planned for surgery. The pathological response rate, tumor regression grade (TRG), and post-surgical complications will be recorded.

The addition of rosuvastatin to NACTRT may improve the oncological outcomes by increasing the likelihood of pCR in patients with locally advanced rectal cancer undergoing NACTRT. This would be a low-cost, low-risk intervention that could potentially lead to the refinement of strategies, such as "watch and wait", in a select subgroup of patients.

Clinical Trials Registry of India, identifier CTRI/2018/11/016459.

The Eastern Canadian Gastrointestinal Cancer Consensus Conference was an annual meeting that was held in St. John's, Newfoundland and Labrador, from 26 to 28 September 2024. This included experts in medical oncology, radiation oncology, surgical oncology, nuclear medicine, and general practitioners in oncology (GPO) from across the eastern Canadian provinces who are involved in the management of patients with gastrointestinal malignancies. This consensus statement generated by the conference addresses multiple topics, including the management of localized rectal cancer, liver-limited colorectal cancer, systemic therapy for advanced biliary tract cancers, radioligand therapy for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), systemic therapy for pancreatic and midgut well-differentiated NETs, and systemic therapy for HER2-positive gastroesophageal cancers.

Rectal cancer surgery has undergone transformative advancements over the past few decades, evolving from radical, high-morbidity procedures to more refined techniques focused on both oncological outcomes and the preservation of anorectal function. This review provides a brief overview of the history of rectal cancer surgery, highlighting key innovations in imaging, neoadjuvant therapy, and minimally invasive techniques that have significantly reduced the need for permanent and temporary ostomies. Additionally, the current indications for both permanent and temporary ostomies are reviewed, including a discussion of associated complications, such as non-reversal, parastomal hernias, stomal prolapse, stenosis, and skin-related issues, along with strategies and techniques to mitigate these complications. This review underscores the importance of ongoing innovation and individualized surgical planning to enhance patient outcomes in rectal cancer care by understanding the historical context, contemporary practices, and associated challenges.

In recent years, new therapeutic approaches have emerged in addition to classical neoadjuvant (chemo)radiotherapy for the treatment of locally advanced rectal cancer (LARC): total neoadjuvant treatment, non-operative management, and radiotherapy-free strategy. While the introduction of these approaches in a relatively short timeframe has quickly increased our therapeutic armamentarium, on the other hand it has complicated the decision-making process regarding the choice of the most appropriate treatment strategy for each patient with LARC. Therefore, a tool to interpret the evidence from clinical trials and to translate them into daily practice is highly demanded. In the present review, we address how these new developments are changing the multimodal treatment of LARC and offer an algorithm to integrate them into clinical practice.

Lateral lymph node dissection (LLND) is an important surgical procedure in the treatment of lower rectal cancer (RC). However, limited data are available regarding the learning curve for robot-assisted LLND (RA-LLND). This study aimed to evaluate the learning curve for prophylactic bilateral RA-LLND for lower RC.

We retrospectively analyzed 58 consecutive patients with clinical stage II/III lower RC who had undergone prophylactic bilateral RA-LLND between July 2020 and June 2024. Cumulative sum (CUSUM) analysis was used to evaluate the learning curve for bilateral RA-LLND operative time.

The mean age of patients was 61.5 years, and mean body mass index was 23.4 kg/m2. The proportion of neoadjuvant therapy was 8.6%. Mean prophylactic bilateral RA-LLND operative time was 173.7 min. CUSUM analysis divided the learning curve for prophylactic bilateral RA-LLND operative time into three phases: initial learning phase (20 cases); competence phase (16 cases); and master/proficiency phase (subsequent cases). Mastery of surgical technique was achieved after performing the 36th case. Comparisons of surgical outcomes in terms of operative parameters and complications were made between phases 1 and 2 combined and phase 3. A significant reduction in mean prophylactic bilateral RA-LLND operative time was observed between phases 1 and 2 compared with phase 3 (P < 0.01). Mean blood loss was decreased in phase 3 (40.5 ml) compared to phases 1 and 2 combined (148.2 ml, P < 0.01). The frequencies of overall postoperative complications directly related to LLND and urinary dysfunction were significantly reduced in phase 3 compared to phases 1 and 2 combined (P = 0.04, and P = 0.02, respectively).

The three phases identified by CUSUM analysis represented characteristics of the learning curve for prophylactic bilateral RA-LLND. These data suggest that 20 cases are required for the early stage of the learning curve, whereas mastery level could be achieved after 36 cases.

With the results of several recently published clinical trials, this guideline focused update provides evidence-based recommendations for the indications and dose-fractionation regimens for neoadjuvant radiation therapy (RT), optimal sequencing of RT and systemic therapy in the context of total neoadjuvant therapy (TNT), and considerations for selective omission of RT and surgery for rectal cancer.

The American Society for Radiation Oncology convened a multidisciplinary task force to update 3 key questions that focused on the role of RT for patients with operable rectal cancer. The key questions addressed (1) indications for neoadjuvant RT, (2) selection of neoadjuvant regimens, and (3) indications for consideration of a nonoperative management (NOM) or local excision approach after definitive/preoperative chemoradiation. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation.

For patients with stage II-III rectal cancer, neoadjuvant RT was strongly recommended; however, among patients deemed at lower risk of locoregional recurrence, consideration of omission of neoadjuvant RT was conditionally recommended in favor of neoadjuvant chemotherapy with a favorable treatment response or upfront surgery. For patients with T3-T4 and node-positive rectal cancer undergoing neoadjuvant RT, a TNT approach was strongly recommended. Among patients with higher risk of locoregional recurrence, TNT with chemotherapy before or after long-course chemoradiation was strongly recommended, whereas TNT with short-course RT followed by chemotherapy was conditionally recommended. For patients with rectal cancer for whom NOM is a priority, concurrent chemoradiation followed by consolidation chemotherapy was strongly recommended. Selection of RT dose-fractionation regimen, sequencing of therapies, and consideration of NOM should be determined by multidisciplinary consensus and based on disease extent, disease location, patient preferences, and quality of life considerations.

The task force proposed recommendations to inform best clinical practices on the use of RT for rectal cancer with strong emphasis on multidisciplinary care. Future studies should focus on further addressing optimal treatment regimens to allow for more personalized recommendations based on individual risk stratification and patient priorities regarding quality of life.

Preoperative radiochemotherapy (RCHT) is the standard of care for locally advanced rectal cancer (LARC). While there are several data regarding chemotherapy intensification, actually, no reliable data directly comparing different radiotherapy (RT) dose levels are available. The present study aimed to compare intensified RT versus standard dose in patients with LARC.

Data from 12 centers were collected for the current large retrospective study. The primary end-point evaluated whether RT dose intensification was associated with an increased pathological complete response (pCR). The secondary end-points explored the relation between RT dose and interval to surgery, downstaging, and RT-related toxicity. Subgroup analysis according to primary tumor stage was also performed.

1028 patients were analysed. All patients received combined RCHT with (364) or without (664) a RT boost. Patients underwent surgery after a median 10 weeks (IQ range 5-28). The overall pCR rate was 21.5 %. In the boost and no-boost groups, the pCR was 26.6 % (97) and 17 % (114) (p = 0.00), respectively. As a subgroup analysis, the pCR stratified by interval to surgery was 10 %, 23 %, 26.3 %, and 39.3 % (p < 0.000) in the boost group versus 10.6 %, 20.8 %, 19.3 %, and 20.4 % (p = 0.018) in the no-boost group. cT3 patients operated on ≥ week 11 and cT4 patients, regardless of time to surgery, received a significant benefit by the RT boost in terms of pCR rate. Patients in the boost group had a higher rate of grade ≥ 3 acute gastrointestinal toxicities (6 % vs. 1.7 %; p = 0.003).

Our results suggest that RT dose intensification (boost) in LARC might significantly increase the pCR rate, although with a small increase in acute toxicity. While pCR seems only partially improved by prolonged time to surgery in the no-boost group, a progressive and significant pCR improvement in patients treated with boost over time was observed. RT boost seems to be beneficial only in more advanced primary tumors.