Active clinical trials for "Rectal Neoplasms"

The primary purpose of this study is to compare the differences of oncological in rectal cancer patients undergoing laparoscopic or transanal endoscopy radical resection. The secondary purpose is to compare the effect of two different surgical methods on prognosis.

Colorectal cancer is common with an annual prevalence of 6000. The majority can be cured and the five year survival rate is over 60%. In december 2019 reports came in about SARS-Cov-2, which later was named Covid-19. The World Health Organization classified it as a pandemic in March 2020. In Sweden the number of patients with Covid-19 increased mainly in the urban areas in March 2020. Care for patients with other diseases were affected and local changes from guidelines were adopted. In some regions and countries the indications for adjuvant and neoadjuvant treatment for colorectal cancer were somewhat changed. The number of patients diagnosed with colorectal cancer also decreased, as well as other types of cancer. The true effect on outcome with a delayed diagnosis remains unknown. The aim of this study is to evaluate the effects of the Covid-19 pandemic on the diagnosis, treatment and survival of patients with colorectal cancer.

In the treatment of locally advanced rectal cancer, the short-term and long-term efficacy of the traditional sandwich regimen has not reached satisfactory efficacy. For this reason, the concept of reducing the dose of postoperative chemotherapy or directly moving forward the full amount of postoperative chemotherapy was proposed, which is called total neoadjuvant therapy (TNT). However, TNT also includes the high toxicity of oxaliplatin in the whole process and the long time interval between the end of radiotherapy and the operation, which leads to fibrosis of the surrounding tissue, which increases the difficulty of surgical resection and makes it difficult to ensure good surgical specimen quality. In addition to this, there are issues that may increase the risk of potential disease progression in patients with poor treatment withdrawal. Therefore, appropriately reducing the intensity of chemotherapy and controlling the total duration of preoperative neoadjuvant therapy during radiotherapy is expected to alleviate the side effects of neoadjuvant therapy. Here, the investigators synthesized the characteristics of TNT and sandwich regimens and proposed a XELOX regimen and capecitabine alternate administration combined with preoperative intensity modulated radiation therapy.

There have been many high-quality research publications, including the TNT model of short-term radiotherapy combined with consolidation chemotherapy, and the TNT model of three-drug combination with neoadjuvant chemotherapy with higher treatment intensity combined with CRT. All have achieved better tumor regression and tumor regression than the standard CRT model. The higher pCR rate reduces the recurrence and metastasis events, improves the prognosis, and strives for more opportunities for organ function preservation. Can the TNT model combined with immunotherapy further increase the cCR rate? Whether immunotherapy can bring further survival benefits to patients who develop CR after neoadjuvant therapy (especially W&W after cCR), it is also necessary to carry out corresponding clinical research. We designed this study for patients with mid-to-low and locally advanced rectal cancer who want to be able to preserve the anus. TNT mode combined with PD-1 immunotherapy is given before surgery, and TME surgery is performed on patients who have not reached cCR or who still require surgery. It provides sufficient evidence for the safety and effectiveness of preoperative neoadjuvant therapy for PD-1 in low- and middle-level locally advanced rectal cancer.

ABSTRACT Background The current management on rectal cancer based on TNM staging has some limitations. In early rectal cancer T stage can be not sufficient to predict the nodal status and, in locally advanced rectal cancer after neoadjuvant therapy the persistence of a complete response to therapy cannot be accurately predicted by the simple tumor regression grade. For both cases the current guidelines recommend the complete rectal resection with a total mesorectal excision. The implications for patients' quality of life are evident even in case of sphincter sparing surgery. Moreover, in both cases the cancer sample available for the analysis can be small or inexistent. Hypothesis The main hypothesis underlying our research is that the aggressiveness of rectal cancer is determined by the complex interactions between the malignant cells and their immune microenvironment. The second hypothesis is that relevant trace of this cross talk between tumor cells and immune microenvironment can be detected in the normal mucosa surrounding the cancer according to the concept of field cancerization. Aims The aim of this project is to analyze the healthy rectal mucosa surrounding the cancer to identify traces of immunosurveillance mechanisms and of field cancerization and to use them to obtain a composite prognostic test to predict nodal metastasis in early rectal cancer and recurrence after complete response at neoadjuvant therapy in case of locally advanced rectal cancer. Experimental Design This prognostic test will be constructed on the combinatory analysis of the transcriptome, immune and epithelial cells cross-talk, immune checkpoints and miRNA expression in normal rectal mucosa surrounding cancer. The aim is to predict the presence of nodal metastasis in patients with early rectal cancer. In step A, we will retrospectively analyze archival tissue samples in order to identify the most performing biomarkers; in step B, we will validate the prognostic performance of the markers identified in phase I through a prospective analysis of rectal mucosa specimen. Expected Results The anticipated outcome of this project is to generate one or different combination of markers to optimize rectal management and to predict rectal cancer patients outcome more accurately than traditional TNM staging or tumore regression grade. We expect to obtain a prognostic test from normal tissue that accurately predicts rectal cancer behavior even in case when the tumor samples are scarce (early rectal cancer) or absent (complete response to therapy) to avoid unnecessary total rectal excision. Impact On Cancer An immunoscore specific for rectal cancer may predict tumor progression and clinical outcome more accurately and may contribute to better design a personalized therapeutic algorithm. Moreover, nowadays patients with early rectal cancer without nodal involvement and patients with potential complete response to neoadjuvant therapy still undergo total rectal excision which is a risky procedure that impairs quality of life. The use of this new prognostic test may make possible to adopt a minimally invasive approach or even simple observation if nodal involvement or residual disease are reasonably excluded.

Background The current management on rectal cancer based on TNM staging has some limitations. In locally advanced rectal cancer after neoadjuvant therapy the persistence of a complete response to therapy cannot be accurately predicted by the simple tumor regression grade. The current guidelines recommend the complete rectal resection with a total mesorectal excision. The implications for patients' quality of life are evident even in case of sphincter sparing surgery. Moreover, in both cases the cancer sample available for the analysis can be small or inexistent. Hypothesis The main hypothesis underlying our research is that the aggressiveness of rectal cancer is determined by the complex interactions between the malignant cells and their immune microenvironment. The second hypothesis is that relevant trace of this cross talk between tumor cells and immune microenvironment can be detected in the normal mucosa surrounding the cancer according to the concept of field cancerization. Aims The aim of this project is to analyze the healthy rectal mucosa surrounding the cancer to identify traces of immunosurveillance mechanisms and of field cancerization and to use them to obtain a composite prognostic test to predict recurrence after complete response at neoadjuvant therapy in case of locally advanced rectal cancer. Experimental Design This prognostic test will be constructed on the combinatory analysis of the transcriptome, immune and epithelial cells cross-talk, immune checkpoints and miRNA expression in normal rectal mucosa surrounding cancer. The project aim is to identify, among locally advanced rectal cancer, those with sustained complete response to neoadjuvant chemo/radiotherapy. The study is articulated in two steps. In step A, we will retrospectively analyze archival tissue samples in order to identify the most performing biomarkers; in step B, we will validate the prognostic performance of the markers identified in phase I through a prospective analysis of rectal mucosa specimen.

Preoperative radiation with single agent chemotherapy as sensitizer is the standard care of locally advanced rectal cancer. Local irradiation significantly increases surgical complications and impairs quality of life. Combination chemotherapy alone seems promising and provides similar benefit to chemoradiation as neoadjuvant therapy. Early administration of systemic therapy is also proved beneficial for long-term survival. The purpose of this study is to compare the efficacy of chemotherapy alone with short-term modified FOLFOXIRI or long-term mFOLFOX with standard chemoradiation as neoadjuvant therapy for locally advanced rectal cancer.

Background: Meta-analyses of large randomized trials proved the superiority of preoperative short course radiation and surgery, as compared with surgery alone. Short course radiation results in a 50% reduction in terms of local relapse in stage II and III rectal cancer patients. Patients with complete pathological remission additionally show a significant survival benefit. Complete pathological remission (pCR) occurs in 8% after preoperative radiation and in >16% if the interval between radiation and surgery is at least 8 weeks. It is generally accepted that mutations in the TP53 gene represent a crucial defect in the apoptosis pathway. Radiation therapy is suggested to act via induction of apoptosis in irradiated cells. Therefore, it is expected that a defect in the TP53 gene has an effect on the success of radiation therapy. Currently available imaging tools are hardly able to diagnose response to radiation therapy correctly, as this does not essentially correlate with tumor size. Method: Aim of this prospective observation study is to strengthen the hypothesis that the TP53 genotype is a promising marker to predict response to radiation therapy in rectal cancer patients. Consequently, the expected results will justify prospective, randomized intervention trials to obtain level of evidence I for the p53 marker hypothesis. Trial endpoint is downstaging and pCR rate. Tumor stage and pathological remission will be evaluated by MRT and pathohistology and correlated to the TP53 genotype of the diagnostic biopsy. Additionally, we will investigate the applicability of novel imaging modalities in magnet resonance tomography to monitor response to radiotherapy. The objective of this study is to evaluate the effect of a genetic tumor marker (TP53 genotype) on the response to preoperative short course radiation (in terms of downstaging and pCR rate) to evaluate the applicability of novel magnet resonance tomography imaging modalities to monitor response to preoperative short time radiation. Conclusion: The prospective evaluation of the potential predictive marker TP53 may bring us one-step closer to an individualized therapy regimen, which allows the restriction of preoperative radiation in rectal cancer to those patients who will benefit.

This study does not involve randomization or treatment. Eligible patients have colorectal adenocarcinoma with no metastases eligible for curative surgery. A pre operative staging scan must have been completed within 6 weeks prior to surgery. Two x 20ml blood samples will be taken from each patient, one prior to and one during or within 24hrs after surgery. Patients are annually followed up to 3 years.

Efficacy of colonoscopy, colon capsule and fecal immunological test for colorectal cancer screening, in first degree relatives of patients with colorectal neoplasia: a prospective randomized study.