Rectal Adenocarcinoma

This clinical trial compares patient (proband)-mediated communication to provider-mediated communication for improving genetic testing in first-degree relatives of patients with newly diagnosed colorectal cancer. It is estimated that 30% of cases of colorectal cancer have a genetic basis and about 15% of these patients have a disease-causing (pathogenic) inherited (germline) variant in a cancer susceptibility gene. Most individuals carrying a pathogenic germline variant are unaware of their cancer risk and may not meet guidelines for genetic testing. Identifying pathogenic germline variants or hereditary cancer syndromes in cancer patients has important implications for their at-risk relatives who may not know that they are at high risk for cancer. The burden of communicating this risk to first-degree relatives often falls on the patients, who may lack sufficient knowledge to correctly share and explain their genetic test results. Receiving provider-mediated communication of genetic testing results may be more effective at communicating genetic risk to first-degree relatives than the usual practice of proband-mediated communication.

To explore the efficacy and safety of short-course radiotherapy combined with mFOLFOX6, PD-1 monoclonal antibody and cetuximab (for RAS/BRAF Wild-Type)/bevacizumab (for RAS/BRAF Mutant) in High-Risk pMMR/MSS Rectal Adenocarcinoma through a prospective study, providing high-level evidence-based medical evidence for the use in the treatment of high-risk rectal cancer.

To explore the efficacy and safety of an intensified treatment regimen consisting of short-course radiotherapy followed by mFOLFOX6 chemotherapy combined with precise targeted therapy (based on RAS/BRAF status: cetuximab for wild-type, bevacizumab for mutant) and a PD-1 monoclonal antibody, compared with short-course radiotherapy followed by mFOLFOX6 chemotherapy alone, in high-risk locally advanced pMMR/MSS rectal adenocarcinoma through a prospective, randomized controlled phase III clinical study, providing high-level evidence-based medical evidence to establish a superior neoadjuvant treatment strategy for this population.

This phase II trial tests how well fluorouracil, oxaliplatin and leucovorin calcium (folinic acid) (FOLFOX) with botensilimab and balstilimab given before surgery (neoadjuvant) works in treating patients with rectal adenocarcinoma that has not spread to other parts of the body (localized). Currently, neoadjuvant therapy for rectal cancer includes chemotherapy and chemoradiation. Despite these aggressive treatments, only about half of patients achieve a complete clinical response. In fact, over half of rectal cancer patients go on to have surgery and often suffer post-surgery complications involving urine and bowel problems. Thus, there has been an increased focus on non-surgical treatments. Chemotherapy drugs, such as fluorouracil, oxaliplatin and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving neoadjuvant FOLFOX with botensilimab and balstilimab may improve the rate of complete response and decrease the need for surgery and radiation therapy in patients with localized rectal adenocarcinoma.

This study adopts a prospective randomized controlled design to evaluate the efficacy and safety of short-course radiotherapy followed by sequential PD-1 inhibitor and FOLFOX chemotherapy versus conventional regimens in high-risk locally advanced pMMR/MSS lower rectal adenocarcinoma, aiming to provide high-level evidence supporting a novel treatment paradigm.

Researchers are looking for other ways to treat locally advanced or metastatic colorectal cancer (mCRC) that is unresectable and has a gene mutation called KRAS G12C. Standard (or usual) treatments for this type of colorectal cancer may include mFOLFOX6 with or without bevacizumab. Researchers want to learn if adding calderasib (the study medicine) and cetuximab to mFOLFOX6 can treat locally advanced or mCRC with the KRAS G12C mutation. Calderasib and cetuximab are targeted therapies. The goals of this study are to learn: * About the safety of calderasib with cetuximab and mFOLFOX6 and if people tolerate the treatments * If people who receive calderasib with cetuximab and mFOLFOX6 live longer without mCRC growing or spreading compared to people who receive mFOLFOX6 with or without bevacizumab.

1.1 Polyps or tumours in the lower part of the bowel (rectum) can be removed using instruments inserted through the bottom which avoids major surgery and the possibility of a stoma bag (colostomy). Afterwards, it is important to check the area with regular camera tests. If checks are delayed, re-growths could be serious and may be untreatable. COVID and other factors have led to long waiting lists for camera checks and in NHS Lothian around 20% of all camera checks are done more than 6 months late. The investigators want to try a new camera and approach that would allow us to reduce waiting lists. Using a short camera called a 'rectoscope' to check the lower bowel has already been shown to be safe, comfortable and acceptable to patients with other conditions. In fact, patients are unlikely to feel or realise any difference between the rectoscope and standard camera tests. The investigators want to show that this 'rectoscope' can be safely used in the outpatient clinic with an enema (suppository) instead of strong bowel medicine taken by mouth the day before. This would mean the camera checks happen on time and would reduce waiting lists for other important tests. The investigators will include 30 patients across three stages of our study. In the first set of patients, the investigators will use the rectoscope alongside the usual endoscope in the endoscopy room using the usual oral bowel medicine. This stage will check the rectoscope is acceptable to the patient and the doctor. In the next 10 patients the investigators will use a suppository instead of oral bowel medicine still using both cameras. Finally, the investigators will use the rectoscope in the outpatient clinic with an suppository to show this is an easy, effective and acceptable way to deliver timely camera checks.

This pilot trial studies how well active surveillance and chemotherapy before surgery work in treating participants with stage II-III rectal cancer. Active surveillance involves monitoring participants for additional tumor growth after receiving cancer treatment. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether deferring surgery after active surveillance and chemotherapy will work better in treating participants with stage II-III rectal cancer.

The study researchers believe that a combination of the drugs trastuzumab and tucatinib, given with standard chemotherapy (capecitabine and oxaliplatin/FOLFOX), may help participants with rectal cancer.

The purpose of this study is to find out whether the study drug, TSR-042, followed by standard chemoradiotherapy (the chemotherapy drug capecitabine + radiation therapy) and standard surgery is an effective treatment for advanced dMMR solid tumors. The study will also look at the safety of the study drug.

This study aims to evaluate the safety and effectiveness of a combination treatment including a PD-1 inhibitor (serplulimab), oncolytic virus H101, short-course radiotherapy, and XELOX chemotherapy as total neoadjuvant therapy in patients with locally advanced low rectal cancer (cT1-3N0M0). In this prospective, multicenter, single-arm phase II study, eligible patients will receive a standardized treatment regimen consisting of intratumoral injection of oncolytic virus H101, short-course radiotherapy, chemotherapy, and immunotherapy over multiple cycles. Tumor response will be assessed using imaging, endoscopy, and clinical evaluation after completion of treatment. The primary objective is to determine the 1-year clinical complete response rate. Secondary outcomes include tumor response rate, organ preservation rate, survival outcomes, and treatment safety. The results of this study may help improve treatment strategies for rectal cancer, increase the rate of complete response, and provide more opportunities for organ preservation while maintaining safety.

To learn if adding metronidazole to standard therapy can decrease populations of Fusobacterium nucleatum (F. nucleatum) and other anaerobes (small organisms that cause infections) in participants with rectal cancer receiving neoadjuvant therapy, compared to neoadjuvant therapy alone.

Rectal cancer patients who do not achieve a complete response to standard of care chemotherapy and radiation often require surgical resection as part of curative intent therapy. This study will evaluate whether additional "focal" radiation delivered internally (rectal brachytherapy) can provide complete responses and thus spare the requirement for surgery. The main questions are whether: 1) rectal brachytherapy is safe in this clinical treatment paradigm and if 2) rectal brachytherapy improves organ preservation (no need for surgery). The trial involves an additional MRI pelvis and sigmoidoscopy with marker placement to define high-risk residual disease for radiation planning. Subsequently, 3 outpatient brachytherapy treatments are given on a weekly basis. If a patient achieves a complete response to brachytherapy, standard of care non-operative surveillance visits are conducted with study visits aligned during the first two years following brachytherapy.

This study evaluates quality of life and utilities following surgical treatment of stage I-IV rectal cancer. This study may help researches learn more about quality of life in patients who have or have had rectal cancer.

This phase I trial investigates how well short-course radiation therapy followed by combination chemotherapy works in treating patients with stage II-III rectal cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as leucovorin, fluorouracil, oxaliplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving short-course radiation therapy and combination chemotherapy may reduce the need for surgery and therefore improve quality of life.

This study is a prospective, open-label, phase I design.

A phase II, single-center, non-profit, interventional study on patients affected by rectal adenocarcinoma. Patients will be stratified into three groups based on pre-treatment clinical stage. The study investigates and may propose a comprehensive, stage-specific, multimodal approach to rectal adenocarcinoma, with a focus on organ preservation even in early stages (cT1-2N0). When organ-sparing strategies are not feasible, the approach prioritizes minimally invasive techniques (laparoscopic and robotic) to reduce the physical, psychological, and quality-of-life impact on patients.

The aim of this study is to evaluate the activity of first-line trastuzumab-deruxtecan, capecitabine and bevacizumab in terms of overall response rate for patients with HER-2 positive metastatic/locally advanced unresectable colorectal cancer

This study evaluates how advanced endoscopic resection techniques affect treatment outcomes in adults with rectal cancer. Rectal cancer has traditionally been treated with standard abdominal surgery. Newer endoscopic techniques allow removal of selected early tumors and may reduce treatment-related complications. However, their effectiveness and safety in tumors with deeper invasion are not yet fully established. This multicenter retrospective observational study uses existing medical records from adults who underwent endoscopic or surgical resection of rectal tumors between 2015 and 2025. Researchers will analyze anonymized information on procedures performed and treatment outcomes to assess the safety and effectiveness of advanced endoscopic approaches. The results of this study may help guide treatment selection and improve care for people with rectal cancer.

This is a phase 2 pragmatic study to examine the utility of ctDNA-informed treatment management for participants with early-stage rectal cancer using the Signatera Genome assay. The primary aims are to 1) assess pathologic complete response (path CR) in the ctDNA informed management arm; 2) assess pathologic complete response (path CR) in the post total neoadjuvant therapy (TNT) standard of care (SOC) surgery arm; and 3) assess disease free survival (DFS) in the ctDNA informed management arm.

Recent research shows that tumour deposits-small spots of cancer found near the main bowel tumour-may give doctors important information about how aggressive the cancer is and how likely it is to come back. Doctors can find tumour deposits either: 1. When looking at scans before surgery, or 2. when examining the removed bowel tissue under the microscope after surgery. In the past, tumour deposits were not always recorded properly. This is because older cancer-staging systems (called TNM 5) used in the UK treated these spots differently, depending on their size, and sometimes labelled them as lymph nodes even when they were not. As a result, many tumour deposits were missed in reports. Since 2018, the UK has been using an updated staging system (called TNM 8) that gives tumour deposits their own category. This means doctors are now expected to report them separately when they are found in the tissue around the bowel. This matters because the investigators know that patients who have tumour deposits may have a higher risk of the cancer returning or spreading. Because of this, these patients might benefit from extra treatment-such as chemotherapy or radiotherapy-on top of surgery. However, if tumour deposits are not routinely recorded on scans or pathology reports, doctors may not realise a patient has them. This means that: 1. Patients may not get the most appropriate advice about their cancer, and 2. Patients may miss out on treatments that could help reduce the chance of the cancer returning. This research project aims to find out two things: 1. Are tumour deposits being routinely reported on scans and pathology reports for rectal cancer since the newer TNM 8 system was introduced? And 2. Is there a link between reporting tumour deposits and another important finding called EMVI (extramural vascular invasion), which also affects cancer behaviour and treatment decisions?

OBJECTIVE Low anterior resection syndrome (LARS) is a term for functional bowel complaints occurring after low anterior resection. Symptoms can range from faecal incontinence and frequent loose stools to urgency and incomplete emptying with great impact on quality of life. Little is known about the longitudinal evolution of LARS and the impact of different schedules of neoadjuvant chemoradiotherapy combined with surgery. The investigators aim to investigate the incidence and evolution of functional bowel complaints in function of different neoadjuvant treatment regimens, type of surgery and adjuvant therapy in patients who undergo surgery for rectal cancer. The investigators focus on following objectives: evolution of LARS- and COREFO-scores per treatment regimen and their impact on work incapacity; identification of possible risk factors potentially related to functional outcome; monitoring and treatment of LARS. METHODS This will be a multicentre prospective interventional study. The study population will consist of adult patients with rectal cancer, regardless of any neo-adjuvant therapy. Patients will be included for 5 years with a 2 year postoperative follow-up. Interim analysis will be made after 2 years of inclusion. Patients with intellectual disability or clinical colon obstruction are excluded. Automated online questionnaires including LARS and COREFO scores, incapacity for work and defecation quality will be sent at different time points (figure 1) using REDCap. RESULTS and CONCLUSIONS Longitudinal change of LARS- and COREFO-scores will be visually summarized. Patient, disease or procedure specific risk factors will be assessed as well. LARS is proven to be the principal postoperative problem after rectal surgery. If the investigators can predict the severity of LARS (minor or major LARS), this can be extremely helpful in deciding whether to perform a sphincter-sparing resection or a rectal amputation instead. Furthermore, the investigators want to offer perspective to patients who are susceptible to a disturbed postoperative bowel function.

This study aims to evaluate the efficacy and safety of short-course radiotherapy combined with CAPOX plus bevacizumab with or without a PD-1 inhibitor in patients with locally advanced rectal cancer (LARC). The hypothesis is that the addition of immunotherapy (PD-1 inhibitor) can significantly improve the complete response (CR) rate and enhance local control while reducing the incidence of distant metastasis. This study will compare the effects of sequential chemoradiotherapy and targeted therapy with or without immunotherapy following short-course radiotherapy, aiming to explore the optimal regimen for total neoadjuvant therapy.

This study measures the levels of circulating tumor DNA (ctDNA) in patients with stage II-III rectal cancer before, during, and after treatment to find out if the presence or absence of ctDNA in patient's blood using the Signatera test can be used to gauge how different treatments may affect rectal cancer. ctDNA is DNA from the rectal cancer that is circulating in the blood. The purpose of this study is to understand if the way rectal tumors respond to standard treatment can be associated with varying levels of ctDNA.

Surgery is the primary treatment for rectal cancer. However, in patients with locally advanced disease, direct surgery often fails to achieve complete tumor resection. In such cases, neoadjuvant therapy is required to downstage the tumor before surgery. The current standard neoadjuvant approach consists of preoperative radiotherapy and then surgery. Although effective, standard radiotherapy uses large target volumes, which results in significant toxicities, increased surgical complications, and reduced patient compliance and quality of life. In addition, excessive radiation fields can compromise the intensity and timing of systemic therapy, potentially increasing the risk of distant metastasis. This may be one of the key reasons why current neoadjuvant radiotherapy mainly improves local control but has not translated into prolonged overall survival. Emerging evidence suggests that combining immunotherapy with radiotherapy may further enhance treatment efficacy. However, large radiation fields may impair the effectiveness of immunotherapy. Therefore, reducing the radiotherapy target volume may not only decrease treatment-related toxicity but also augment the immunotherapy response. This clinical study is designed to evaluate whether reducing the radiotherapy target volume, when combined with chemotherapy and immunotherapy prior to surgery, can decrease radiotherapy-related toxicities and reduce the risk of distant metastasis, without increasing the local recurrence rate, compared with the current standard radiotherapy fields. The ultimate goal is to improve the efficacy of neoadjuvant therapy in locally advanced rectal cancer while minimizing treatment toxicity, thereby providing new strategies and evidence for preoperative management.