Radiotherapy For Rectal Cancer Research Articles

Proton radiotherapy for rectal cancer

AIM: to assess the effectiveness of proton radiotherapy as part of a combined approach to the treatment of rectal malignancies and to assess acute radiation toxicity, which directly affects patients’ quality of life.PATIENTS AND METHODS: between 2020 and 2023, a study included 74 patients with rectal cancer. The mean age of the patients was 65 ± 9.9 years, 44 (60%) males. Stage I occurred in 8 (10.8%) patients, stage II — in 14 (18.9%) patients, stage III — in 52 (70.3%) patients. At the first stage, all patients completed proton radiation therapy in the classical fractionation mode.RESULTS: of the adverse events, 49 (66%) patients had grade 1–2 radiation reactions in the form of proctitis and cystitis. There were no local radiation reactions of grade 3 or higher. Systemic complications of grade 3 were noted in 2 (2%) patients in the form of hematological toxicity — anemia (1%), afebrile neutropenia (2%). Of the 62 operated patients, 12 (19.3%) people showed complete therapeutic pathomorphosis. With a median follow-up of 23 months (13;35), 1 (1.35%) patient showed continued tumor growth 28 months after completed radiotherapy, 2 (2.7%) patients had local recurrence 3 and 18 months after treatment. Distant metastases to the lungs, liver, or bones were detected in 9 (12.2%) patients, median — 12 months (6;23). Mortality during the entire observation period was 9 (12.2%) patients. Sixty-two (83.8%) patients showed no signs of relapse or progression of the disease, of which 9 (14.5%) patients did not receive any treatment after chemoradiotherapy and are in the process of active follow-up.CONCLUSION: proton radiation therapy in patients with rectal cancer in two-year overall survival (90.5%) and progression-free survival (88.9%) are comparable with the literature data of recent studies, but are superior in overall survival pathological response (19.3%).

Utero-Ovarian “out of field” Transposition Before Pelvic Radiation in a Patient with Rectal Cancer: A First Swiss Experience

Abstract Background Colorectal cancer represents the third most common cancer and the second leading cause of cancer-related mortality worldwide. The incidence of rectal cancer is rising faster and is increasing among young adults. Due to advances in diagnosis and treatment, most young patients with rectal cancer present long-term survival. Treatment-related infertility represents a largely unaddressed problem. Fertility preservation is essential in managing young women requiring chemo- and radiotherapy for rectal cancer. Ovaries and oocytes are very sensitive to radiation and chemotherapeutic agents, and current fertility preservation strategies include oocytes, embryos, or ovarian tissue cryopreservation and ovarian transposition out of the radiation field. Nevertheless, patients have little probability of procreating due to irreversible uterine radiation damages. Utero-ovarian “out of filed” Transposition [UOT] represent an interesting perspective specially in countries were pregnancy surrogacy is not allowed. Aims Demonstrate feasibility of an innovative surgical procedure permitting uterine functional preservation after long course neoadjuvant therapy for low rectal cancer including total chemo and radio-chemotherapy. Methods First Clinical Swiss experience case presentation. In addition, of a systematic review of the literature available to date on all cases of UOT was realized, and 13 patients from 9 articles were included. Results A 28-year-old nulligravida patient was diagnosed with a low-grade rectal adenocarcinoma. Before neoadjuvant therapies, the patient underwent laparoscopic UOT. The intervention was performed without complications, and the patient received neoadjuvant treatments as planned. TaTME and uterus repositioning were completed six weeks after the radiotherapy's end. No complications were observed during the first 9 postoperative months. Adequate utero-ovarian perfusion was assessed by Doppler ultrasound, cervicovaginal anastomosis appeared healed correctly, and the patient experienced menstrual bleeding. Data from the literature review of reported cases of UOT were presented. Conclusion UOT represents a valuable option to preserve fertility in patients requiring pelvic radiotherapy. This study provides additional evidence on the feasibility and safety of UOT.

An International Expert-Based Consensus on the Definition of a Clinical Near-Complete Response After Neoadjuvant (Chemo)radiotherapy for Rectal Cancer.

A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to inconsistency in clinical practice, long-term outcome, and trial enrollment. The aim of this study was to reach expert-based consensus on the definition of a clinical near-complete response after (chemo) radiotherapy. A modified Delphi process, including a systematic review, 3 surveys, and 2 meetings, was performed with an international expert panel consisting of 7 surgeons and 4 radiologists. The surveys consisted of individual features, statements, and feature combinations (endoscopy, T2-weighted MRI, and diffusion-weighted MRI). The modified Delphi process was performed in an online setting; all 3 surveys were completed online by the expert panel, and both meetings were hosted online. The main outcome was to reach consensus (80% or more agreement). The expert panel reached consensus on a 3-tier categorization of the near-complete response category based on the likelihood of the response to evolve into a clinical complete response after a longer waiting interval. The panelists agreed that a near-complete response is a temporary entity only to be used in the first 6 months after (chemo)radiotherapy. Furthermore, consensus was reached that the lymph node status should be considered when deciding on a near-complete response and that biopsies are not always needed when a near-complete response is found. No consensus was reached on whether primary staging characteristics have to be taken into account when deciding on a near-complete response. This 3-tier subcategorization is expert-based; therefore, there is no supporting evidence for this subcategorization. Also, it is unclear whether this subcategorization can be generalized into clinical practice. Consensus was reached on the use of a 3-tier categorization of a near-complete response, which can be helpful in daily practice as guidance for treatment and to inform patients with a near-complete response on the likelihood of successful organ preservation. See Video Abstract. ANTECEDENTES:Actualmente, se utilizan una variedad de definiciones para una respuesta clínica casi completa después de quimioradioterapia neoadyuvante contra el cáncer de recto. Esta variedad resulta en inconsistencia en la práctica clínica, los resultados a largo plazo y la inscripción en ensayos.OBJETIVO:El objetivo de este estudio fue llegar a un consenso de expertos sobre la definición de una respuesta clínica casi completa después de quimioradioterapia.DISEÑO:Se realizó un proceso Delphi modificado que incluyó una revisión sistemática, 3 encuestas y 2 reuniones con un panel internacional de expertos compuesto por siete cirujanos y 4 radiólogos. Las encuestas consistieron en características individuales, declaraciones y combinaciones de características (endoscopía, T2W-MRI y DWI).AJUSTE:El proceso Delphi modificado se realizó en un entorno en línea; el panel de expertos completó las tres encuestas en línea y ambas reuniones se realizaron en línea.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue llegar a un consenso (≥80% de acuerdo).RESULTADOS:El panel de expertos llegó a un consenso sobre una categorización de tres niveles de la categoría de respuesta casi completa basada en la probabilidad de que la respuesta evolucione hacia una respuesta clínica completa después de un intervalo de espera más largo. Los panelistas coincidieron en que una respuesta casi completa es una entidad temporal que sólo debe utilizarse en los primeros 6 meses después de la quimioradioterapia. Además, se llegó a un consenso en que se debe considerar el estado de los nódulos linfáticos al decidir sobre una respuesta casi completa y que no siempre se necesitan biopsias cuando se encuentra una respuesta casi completa. No se llegó a un consenso sobre si se deben tener en cuenta las características primarias de estadificación al decidir una respuesta casi completa.LIMITACIONES:Esta subcategorización de 3 niveles está basada en expertos; por lo tanto, no hay evidencia que respalde esta subcategorización. Además, no está claro si esta subcategorización puede generalizarse a la práctica clínica.CONCLUSIONES:Se alcanzó consenso sobre el uso de una categorización de 3 niveles de una respuesta casi completa que puede ser útil en la práctica diaria como guía para el tratamiento y para informar a los pacientes con una respuesta casi completa sobre la probabilidad de una preservación exitosa del órgano. (Traducción - Dr. Aurian Garcia Gonzalez).

Live birth from ovarian grafted tissue after pelvic radiation for rectal cancer

ObjectiveTo study the management of a woman who returned to conceive after high dose radiation treatment (RT), with documentation of uterine dosimetry, and the efficacy of ovarian tissue grafted into an irradiated pelvis. Design, setting, interventionA 26-year-old woman underwent RT to treat rectal cancer, with half of the uterus being exposed to a radiation dose of 50 Gy and 25 Gy to the fundus. We report details of the uterine assessment, determining suitability of conception with her own uterus, pregnancy surveillance and reproductive outcome. Main outcome measures, resultsThe results of MRI and pelvic ultrasound showed a small uterus with preserved junctional zone anatomy and while the endometrium was initially thin following administration of high oestrogen administration, endometrial thickness increased with time. Twelve grafted ovarian tissue stimulation cycles led to 4 embryo transfers, the last of which resulted in a live birth. She had two cervical cerclage procedures due to cervical shortening and delivered a 3.3kg healthy girl at 38/40 via LSCS. ConclusionsSuccessful pregnancy is possible from ovarian tissue grafted into an irradiated pelvis, with high dose uterine exposure. Careful uterine assessment needs to be undertaken to determine suitability of conception attempt with a patient’s own uterus, in consultation with the medical team. Further studies are needed to correlate imaging and biopsy findings with reproductive outcomes.

Surgical Outcomes after Radiotherapy in Rectal Cancer.

Over the past decade, the treatment of rectal cancer has changed considerably. The implementation of TME surgery has, in addition to decreasing the number of local recurrences, improved surgical morbidity and mortality. At the same time, the optimisation of radiotherapy in the preoperative setting has improved oncological outcomes even further, although higher perineal infection rates have been reported. Radiotherapy regimens have evolved through the adjustment of radiotherapy techniques and fields, increased waiting intervals, and, for more advanced tumours, adding chemotherapy. Concurrently, imaging techniques have significantly improved staging accuracy, facilitating more precise selection of advanced tumours. Although chemoradiotherapy does lead to the downsizing and -staging of these tumours, a very clear effect on sphincter-preserving surgery and the negative resection margin has not been proven. Aiming to decrease distant metastasis and improve overall survival for locally advanced rectal cancer, systemic chemotherapy can be added to radiotherapy, known as total neoadjuvant treatment (TNT). High complete response rates, both pathological (pCR) and clinical (cCR), are reported after TNT. Patients who follow a Watch & Wait program after a cCR can potentially avoid surgical morbidity and colostomy. For both early and more advanced tumours, trials are now investigating optimal regimens in an attempt to offer organ preservation as much as possible. Multidisciplinary deliberation should include patient preference, treatment toxicity, and likelihood of end colostomy, but also the burden of intensive surveillance in a W&W program.

Abstract CT130: Epacadostat with preoperative chemoradiation in locally advanced rectal cancer (LARC): Results of a translational phase I clinical trial

Abstract BACKGROUND: In preclinical studies, we found that the immuno-oncology target and tryptophan metabolizing enzyme indoleamine 2, 3-dioxygenase 1 (IDO1) promotes resistance to radiation in rectal cancer regardless of MSI status. Furthermore, IDO1 inhibition with epacadostat improved tumor radiosensitivity, abrogated immunosuppression, limited distal recurrence, and was radioprotective of the normal intestine. This trial aimed to evaluate the safety of IDO1 inhibition when combined with neoadjuvant short-course radiation (SCRT) and chemotherapy with capecitabine and oxaliplatin (CAPOX) for LARC. METHODS: The primary objective was to determine the recommended phase II dose (RP2D) of epacadostat for combination with SCRT and CAPOX. Secondary objectives included determining antitumor activity as measured by neoadjuvant rectal (NAR) score and pathological or clinical complete responses. During the dose escalation phase, 3 doses of epacadostat (300mg, 400mg, & 600mg BID) were explored. Epacadostat was combined with SCRT (5Gy x 5 fractions) followed by 6 cycles of CAPOX chemotherapy, until the day of surgery (~24 wks). Tissues and blood were collected for correlative studies. A control cohort was generated from patients receiving the same treatment without epacadostat. NCT03516708 RESULTS: Seventeen patients were enrolled from 4/2019 to 8/2023. RP2D of epacadostat in combination with SCRT and CAPOX chemotherapy was determined to be 400mg BID. Two patients experienced dose-limiting toxicities (DLT) at 600mg dose level, one with G2 elevated ALT and another with G3 maculopapular rash. No DLT was reported at other dose levels. Of six patients who underwent surgery, the mean NAR score was 7.46 (SD 7.11; range 0 - 20.4), indicating potentially better response compared to the mean NAR of 17.8 in an institutional 2:1 matched control cohort (p=0.03). Tumor tissue revealed increased IDO1 expression and kynurenine levels in all patient tumors after radiation. After epacadostat, serum levels of kynurenine were reduced while TNFα, IFNγ, and MIP1a were all increased. Global metabolomics and RNAseq revealed a distinct pattern of serum biomarkers and immunophenotype respectively in patients after treatment. Tumoroids were evaluated as ex vivo models of treatment response. CONCLUSION: Epacadostat in combination with SCRT and CAPOX was well-tolerated. An NCI supported Phase 2 trial is ongoing to further evaluate the promising disease responses reported in dose escalation phase. Citation Format: Haeseong Park, Katrina Pedersen, Katherine Huang, Matthew Mutch, Hyun Kim, Nikolaos Trikalinos, Olivia Aranha, Benjamin Tan, Rama Suresh, Lee Ratner, Moh'd Khushman, John Visconti, Kian-Huat Lim, Lauren Henke, Maddie Swiecicki, Jingxia Liu, Parag Parikh, Matthew Ciorba. Epacadostat with preoperative chemoradiation in locally advanced rectal cancer (LARC): Results of a translational phase I clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT130.

Exploration of the method and efficacy of treatments for intractable pelvic pain caused by rectal or bladder fistula

Objective: To explore the causes and therapeutic effects of pelvic pain caused by rectal fistula or bladder fistula after comprehensive treatment of cervical cancer and rectal cancer (radiotherapy, surgery, chemotherapy, and other treatments). Methods: A retrospective analysis was conducted on the clinical and pathological data of patients with pelvic tumors admitted to the First People's Hospital of Yinchuan City, Ningxia and the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to June 2022. The causes of persistent pelvic pain in patients after comprehensive treatment was investigated, and the corresponding therapeutic effects after clinical treatment was observed. Results: Thirty-two tumor patients experienced persistent pain after comprehensive treatment, including 22 cases of cervical cancer and 10 cases of rectal cancer. The preoperative pain of the entire group of patients was evaluated using the digital grading method, with a pain score of (7.88±1.31) points. Among the 32 patients, there were 16 cases of rectovaginal fistula or ileovaginal fistula, 9 cases of vesicovaginal fistula, 5 cases of rectoperineal fistula, and 2 cases of vesicovaginorectal fistula. Thirty-two patients were initially treated with medication to relieve pain, and according to the ruptured organs, a fistula was made to the corresponding proximal intestinal canal and renal pelvis to intercept the intestinal contents and urine. However, the pain did not significantly be improved. The pain score of treatment with the above methods for one week was (8.13±1.13) points, and there was no statistically significant difference compared to preoperative treatment (P=0.417). In the later stage, based on a comprehensive evaluation of whether the tumor had recurred, the value of organ preservation, the benefits of surgery, the balance between survival time and improving quality of life, pathological organ resection or repair was performed. The surgical methods included repair of leaks, local debridement combined with irrigation of proximal intestinal fluid, distal closure of the sigmoid colon combined with proximal ostomy, posterior pelvic organ resection, anterior pelvic organ resection, and total pelvic organ resection. One week after surgery, the patients' pain completely relieved or disappeared, with the pain score of (1.72±1.37) points, which was significantly divergent from the preoperative and initial surgical treatments (P＜0.001). Conclusions: Palliative pyelostomy and proximal enterostomy cannot effectively alleviate persistent pelvic floor pain. The fundamental way to alleviate pain is complete blocking of the inflammatory erosion of the intestinal fluid and urine.

Evolution of clinical nature, treatment and survival of locally recurrent rectal cancer: Comparative analysis of two national cross-sectional cohorts

BackgroundIn the Netherlands, use of neoadjuvant radiotherapy for rectal cancer declined after guideline revision in 2014. This decline is thought to affect the clinical nature and treatability of locally recurrent rectal cancer (LRRC). Therefore, this study compared two national cross-sectional cohorts before and after the guideline revision with the aim to determine the changes in treatment and survival of LRRC patients over time. MethodsPatients who underwent resection of primary rectal cancer in 2011 (n = 2094) and 2016 (n = 2855) from two nationwide cohorts with a 4-year follow up were included. Main outcomes included time to LRRC, synchronous metastases at time of LRRC diagnosis, intention of treatment and 2-year overall survival after LRRC. ResultsUse of neoadjuvant (chemo)radiotherapy for the primary tumour decreased from 88.5% to 60.0% from 2011 to 2016. The 3-year LRRC rate was not significantly different with 5.1% in 2011 (n = 114, median time to LRRC 16 months) and 6.3% in 2016 (n = 202, median time to LRRC 16 months). Synchronous metastasis rate did not significantly differ (27.2% vs 33.7%, p = 0.257). Treatment intent of the LRRC shifted towards more curative treatment (30.4% vs. 47.0%, p = 0.009). In the curatively treated group, two-year overall survival after LRRC diagnoses increased from 47.5% to 78.7% (p = 0.013). ConclusionPrimary rectal cancer patients in 2016 were treated less often with neoadjuvant (chemo)radiotherapy, while LRRC rates remained similar. Those who developed LRRC were more often candidate for curative intent treatment compared to the 2011 cohort, and survival after curative intent treatment also improved substantially.

Excluding external iliac node irradiation during neoadjuvant radiotherapy decreases lower intestinal toxicity without compromising efficacy in T4b rectal cancer patients with tumours involving the anterior structures

PurposeTo explore the impact of excluding the external iliac node (EIN) from the clinical target volume (CTV) during preoperative radiotherapy in T4b rectal cancer with anterior structure invasion.MethodsWe retrospectively identified 132 patients with T4b rectal cancer involving the anterior structures who received radiotherapy followed by surgery between May 2010 and June 2019. Twenty-nine patients received EIN irradiation (EIN group), and 103 did not (NEIN group). Failure patterns, survival and toxicities were compared between the two groups.ResultsThe most common failure was distant metastasis (23.5%). 11 (8.3%) patients developed locoregional recurrence, 10 (9.7%) patients were in the NEIN group, and 1 (3.4%) was in the EIN group (P = 0.34). The EIN region failure was rare (1/132, 0.8%). The locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 96.3% vs. 90.5%, 82.1% vs.73.7%, 75.9% vs. 78.0% and 72.4% vs. 68.3% (all P > 0.05) for the EIN group and NEIN group, respectively. The incidence of grade 3–4 acute toxicity in the lower intestine was significantly higher in the EIN group than in the NEIN group (13.8% vs. 1.9%, P = 0.02). The Dmax, V35 and V45 of the small bowel was decreased in the NEIN group compared to the EIN group.ConclusionsExclusion of the EIN from the CTV in T4b rectal cancer with anterior structure invasion could reduce lower intestinal toxicity without compromising oncological outcomes. These results need further evaluation in future studies.

Robotic-assisted uterine transposition followed by anatomic pelvic repositioning for a patient with intramural fibroids and rectal cancer

To report the first described case of robotic-assisted utero-ovarian transposition followed by anatomic repositioning in the pelvis and cervico-vaginal anastomosis in a woman with uterine fibroids, which was performed for fertility preservation in the context of pelvic radiation for rectal cancer. Description of technique and live-action narrated surgical footage showing uterine transposition and repositioning. 36 year-old woman with a new diagnosis of cT3N2M0 rectal adenocarcinoma, planned for neoadjuvant chemotherapy and pelvic radiation, who desired fertility preservation permissive of future pregnancy. Transvaginal ultrasound revealed a 5-cm posterior leiomyoma and normal endometrial cavity. The patient elected for utero-ovarian transposition prior to chemoradiation. The patient included in this video gave consent for publication and posting of the video online including social media, the journal website, scientific literature websites and other applicable sites. Per institutional guidelines, IRB review was not required. Robotic-assisted utero-ovarian transposition was performed in an inpatient setting two weeks following ovarian stimulation and oocyte retrieval. She was given GnRH agonist for menstrual suppression after oocyte retrieval. The uterus and adnexa were transposed en bloc to the upper abdomen, with perfusion via retroflected infundibulopelvic ligaments. Intravenous indocyanine green (ICG) was administered intraoperatively to visualize uterine perfusion. Three weeks postoperatively, the patient underwent surgical management of small bowel obstruction, which was successfully managed with laparoscopic adhesiolysis. The patient subsequently completed chemoradiation, and had complete response of rectal tumor. She therefore elected for surveillance. Seven months following transposition, and two months following completion of treatment, the patient underwent uncomplicated robotic-assisted utero-ovarian anatomic repositioning in the pelvis with cervico-vaginal anastomosis. Chromopertubation confirmed tubal patency. Restoration of normal pelvic anatomy, resumption of reproductive physiology RESULTS: At her 4-month postoperative visit, the cervix and vagina were normal in appearance. The patient reported return of spontaneous menses and sexual activity without complication. This case is unique due to the presence of bulky intramural uterine fibroids. The described technique may be useful for select cancer patients, who desire to carry a pregnancy following pelvic radiation for cancer treatment, and demonstrates that patients considering utero-ovarian transposition need not be excluded solely based on presence of uterine fibroids.

Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer.

Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR] = 0.3 in the targeted sequencing and OR = 0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR = 6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, non-responding tumors with initially small sizes carried a higher risk of recurrence. The findings, even if limited in addition to the imperfect clinical factors, offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.

The recovery of intestinal barrier function and changes in oral microbiota after radiation therapy injury.

Colorectal cancer (CRC) is the third most common malignant tumor, and neoadjuvant chemo-radiotherapy is usually recommended for advanced stage colorectal cancer. Radiotherapy can cause damage to intestinal mucosal barrier, which may be related to perioperative complications. Intestinal microbiota is one of the constituents of the intestinal mucosal biological barrier, and literature reports that patients with CRC have changes in corresponding oral microbiota. This study aims to analyze the levels of immunoglobulin SIgA, inflammatory factors, lymphocyte subsets quantity, and proportion in surgical specimens of intestinal mucosa at different time intervals after radiotherapy, in order to seek investigation for the optimal surgical time after radiotherapy and to provide evidence for finding probiotics or immunomodulators through high-throughput sequencing of bacterial 16s rRNA in patients' saliva microbiota. Ultimately, this may provide new ideas for reducing perioperative complications caused by radiotherapy-induced intestinal damage. We selected intestinal mucosal tissue and saliva samples from over 40 patients in our center who did not undergo radiotherapy and underwent surgery at different time intervals after radiotherapy. Detection of SIgA was performed using ELISA assay. Western Blotting was used to detect IL-1β, IL-6, and IL-17 in the intestinal mucosal tissue. Flow cytometry was used to detect CD4 and CD8. And the microbial community changes in saliva samples were detected through 16s rRNA sequencing. After radiotherapy, changes in SIgA, various cytokines, CD4CD8 lymphocyte subsets, and oral microbiota in the intestinal mucosal tissue of rectal cancer patients may occur. Over time, this change may gradually recover. In colorectal cancer, oncological aspects often receive more attention, while studies focusing on the intestinal mucosal barrier are less common. This study aims to understand the repair mechanisms of the intestinal mucosal barrier and reduce complications arising from radiotherapy-induced damage. The relationship between oral microbiota and systemic diseases has gained interest in recent years. However, the literature on the oral microbiota after radiotherapy for rectal cancer remains scarce. This study addresses this gap by analysing changes in the salivary microbiota of rectal cancer patients before and after radiotherapy, shedding light on microbiota changes. It aims to lay the groundwork for identifying suitable probiotics or immunomodulators to alleviate perioperative complications and improve the prognosis of CRC.

Trends and Variation in the Use of Radiotherapy in Non-metastatic Rectal Cancer: a 14-year Nationwide Overview from the Netherlands

AimsThis study describes nationwide primary radiotherapy utilisation trends for non-metastasised rectal cancer in the Netherlands between 2008 and 2021. In 2014, both colorectal cancer screening and a new guideline specifying prognostic risk groups for neoadjuvant treatment were implemented. Materials and methodsPatients with non-metastasised rectal cancer in 2008–2021 (n = 37 510) were selected from the Netherlands Cancer Registry and classified into prognostic risk groups. Treatment was studied over time and age. Multilevel logistic regression analyses were carried out to identify factors associated with (i) radiotherapy versus chemoradiotherapy use for intermediate rectal cancer and (ii) chemoradiotherapy without versus with surgery for locally advanced rectal cancer. ResultsFor early rectal cancer, the use of neoadjuvant radiotherapy decreased (15% to 5% between 2008 and 2021), whereas the use of endoscopic resections increased (8% in 2015, 17% in 2021). In intermediate-risk rectal cancer, neoadjuvant chemoradiotherapy (43% until 2011, 25% in 2015) shifted to radiotherapy (42% in 2008, 50% in 2015), the latter being most often applied in older patients. In locally advanced rectal cancer, the use of chemoradiotherapy without surgery increased (2–4% in 2008–2013, 17% in 2019–2021). Both neoadjuvant treatment in intermediate disease and omission of surgery following chemoradiotherapy in locally advanced disease varied with increasing age (odds ratio>75vs<50: 2.17, 95% confidence interval 1.54–3.06) and treatment region (Southwest and Northwest odds ratio 0.63, 95% confidence interval 0.42–0.93 and odds ratio 0.65, 95% confidence interval 0.44–0.95, respectively, compared with the North). ConclusionTreatment patterns in non-metastasised rectal cancer significantly changed over time. Effects of both the national screening programme and the new treatment guideline were apparent, as well as a paradigm shift towards organ preservation (watch-and-wait). Observed regional variations may indicate adoption differences regarding new treatment strategies.

Rectal cancer disparities in a large, diverse health system in New York.

16 Background: The disproportionate burden of colorectal cancer among African American (AA) patients is striking, with 40% increase relative risk of death compared to non-AA White population (Seer Cancer Statistics Review, 2022). NAPRC aims to ensure equitable delivery of evidence-based treatment to ensure optimal outcomes for all patients. Our study investigated whether care delivery outcomes differed for AA patients in our NAPRC cohort of patients, and explored the reasons associated with the disparities. Methods: Rectal cancer patients were identified by pooling 2019 to 2022 data from NAPRC coordinators from 4 regional sites under Northwell Health, spread across a large geographical area in NY: Westchester and Phelps (Northern), Lenox Hill (Western), NSUH/LIJ (Central), and Huntington (Eastern). The primary outcome was time from biopsy (Bx) to treatment (Tx) initiation, where Tx was rectal cancer resection, chemotherapy, or radiotherapy. The secondary outcome was time from tumor board (TB) to first Tx. Social deprivation index (SDI) is a composite measure of 7 demographic characteristics collected in the American Community Survey (ACS) matched with zip codes of patients. SDI and the deprivation severity have a positive and linear correlation. Results: We collected data on 381 patients; 337 had documented race data: 42 AA and 295 non-AA (includes White, Asians and others). AA, compared to non-AA, patients had significantly longer median time from Bx to Tx in Western (66 vs 42 days, p&lt;0.01) and Central (56 vs 41 days, p= 0.03) regions. AA patients also had higher time from TB to Tx in the Western (29 vs 17 days, p=0.01) and Central (26 vs 19 days, p= 0.05) regions, respectively. Longer time to treatment was associated with: AA patients, Medicare patients, and patients requiring social work assistance. SDI is positively correlated with time from Bx to Tx (p&lt;0.01) and time from TB to Tx (p&lt;0.01). Conclusions: There are significant disparities between AA vs Non-AA in both primary and secondary outcomes. These findings highlight the need for further exploration such as interviewing social workers and developing patient surveys to explore why the care disparities in AA population is more significant in certain regions than others. We need to account for race and social barriers in treating cancer patients. Taking a proactive approach by sending social work referrals for all AA patients may be a potential solution for these marginalized patients.

Radiation-induced changes in gene expression in rectal cancer specimens.

The standard-of-care for locally advanced rectal cancer is radiotherapy-based neoadjuvant therapy followed by surgical resection. This article reviews the evidence of molecular changes at the transcriptome level induced through radiotherapy in rectal cancer. The PubMed search "(radiation OR radiotherapy) cancer (transcriptome OR "gene expression") rectal" was used. The studies taken forward utilised gene-expression data on both pre-treatment and post-treatment rectal adenocarcinoma biospecimens from patients treated with RT-based neoadjuvant strategies. Twelve publications met the review criteria. There was variation in approaches in terms of design, patient population, cohort size, timing of the post-radiotherapy sampling and method of measuring gene expression. Most of the post-treatment biospecimen retrievals were at resection. The literature indicates a broad upregulation of immune activity through radiotherapy using gene-expression data. Future studies would benefit from standardised prospective approaches to sampling to enable the inclusion of timepoints relevant to the tumour and immune response.

Research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi-omics

BackgroundRadiosensitivity of rectal cancer is related to the radiotherapy efficacy and prognosis of patients with rectal cancer, and the genes and molecular mechanisms related to radiosensitivity of rectal cancer have not been clarified. We explored the radiosensitivity related genes of rectal cancer at a multi omics level.MethodsmRNA expression data and rectum adenocarcinoma (READ) data were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus Database (GEO) (GSE150082, GSE60331, GSE46862, GSE46862). Differentially expressed genes between radiotherapy sensitive group and radiotherapy insensitive group were screened. GO analysis and KEGG pathway analysis were performed for differentially expressed genes. Among the differentially expressed genes, five core genes associated with rectal cancer prognosis were selected using random survival forest analysis. For these five core genes, drug sensitivity analysis, immune cell infiltration analysis, TISIDB database immune gene correlation analysis, GSEA enrichment analysis, construction of Nomogram prediction model, transcriptional regulatory network analysis, and qRT-PCR validation was performed on human rectal adenocarcinoma tissue.ResultsWe found that 600 up-regulated genes and 553 down-regulated genes were significantly different between radiotherapy sensitive group and radiotherapy insensitive group in rectal cancer. Five key genes, TOP2A, MATR3, APOL6, JOSD1, and HOXC6, were finally screened by random survival forest analysis. These five key genes were associated with different immune cell infiltration, immune-related genes, and chemosensitivity. A comprehensive transcriptional regulatory network was constructed based on these five core genes. qRT-PCR revealed that MATR3 expression was different in rectal cancer tissues and adjacent non-cancerous tissues, while APOL6, HOXC6, JOSD1, and TOP2A expression was not different.ConclusionFive radiosensitivity-related genes related to the prognosis of rectal cancer: TOP2A, MATR3, APOL6, JOSD1, HOXC6, are involved in multiple processes such as immune cell infiltration, immune-related genes, chemosensitivity, signaling pathways and transcriptional regulatory networks and may be potential biomarkers for radiotherapy of rectal cancer.

Radiological Biomarkers in MRI directed Rectal Cancer Radiotherapy Volume Delineation.

Our study evaluated whether an MRI reporting system highlighting areas of contiguous and discontinuous extramural venous invasion (EMVI) can improve the accuracy of gross tumour volume (GTV) delineation. Initially, 27 consecutive patients with locally advanced rectal cancer treated between 2012 and 2014 were evaluated. We used an MRI reporting proforma that documented the position of the primary tumour, lymph nodes and EMVI. The new GTVs delineated were compared with historical radiotherapy treatment volumes to identify the frequency of GTV geographical miss. We observed that the delineation of involved nodes and areas of EMVI was more likely to represent sources of uncertainty wherein nodal GTV geographical miss was evident in 5 out of 27 patients (19%). Complete EMVI GTV geographical miss occurred in two patients (7%). We re-evaluated our radiotherapy practice in a further 27 patients after the implementation of a modified MRI reporting system. An improvement was seen; nodal miss was observed in two patients (7%) and partial EMVI miss in one patient (4%), although these areas were encompassed in the planning target volume (PTV). Our study shows that extramural venous invasion and involved nodes need to be highlighted on MRI to improve the accuracy of rectal cancer GTV delineation.

A Modified NAR Scoring Model Incorporating Immune Infiltration Characteristics to Better Predict Long-Term Survival Following Neoadjuvant Radiotherapy in Rectal Cancer.

(1) Background: The neoadjuvant rectal (NAR) score has been developed as a prognostic tool for survival in locally advanced rectal cancer (LARC). However, the NAR score only incorporates weighted cT, ypT, and ypN categories. This long-term follow-up study aims to modify a novel prognostic scoring model and identify a short-term endpoint for survival. (2) Methods: The prognostic factors for overall survival (OS) were explored through univariate and multivariate analyses. Based on Cox regression modeling, nomogram plots were constructed. Area under the curve (AUC) and concordance indices were used to evaluate the performance of the nomogram. Receiver operating characteristic (ROC) analysis was conducted to compare the efficiency of the nomogram with other prognostic factors. (3) Results: After a long-term follow-up, the 5-year OS was 67.1%. The mean NAR score was 20.4 ± 16.3. Multivariate analysis indicated that CD8+ T-cell, lymphovascular invasion, and the NAR score were independent predictors of OS. The modified NAR scoring model, incorporating immune infiltration characteristics, exhibited a high C-index of 0.739 for 5-year OS, significantly outperforming any individual factor. Moreover, the predictive value of the nomogram was superior to the AJCC stage and pathological complete regression at 3-year, 5-year, and 10-year time points, respectively. Over time, the model's predictions of long-term survival remained consistent and improved in accuracy. (4) Conclusions: The modified NAR scoring model, incorporating immune infiltration characteristics, demonstrates high accuracy and consistency in predicting OS.

Implications of Rectal Cancer Radiotherapy on the Immune Microenvironment: Allies and Foes to Therapy Resistance and Patients’ Outcome

Aside from surgical resection, locally advanced rectal cancer is regularly treated with neoadjuvant chemoradiotherapy. Since the concept of cancer treatment has shifted from only focusing on tumor cells as drivers of disease progression towards a broader understanding including the dynamic tumor microenvironment (TME), the impact of radiotherapy on the TME and specifically the tumor immune microenvironment (TIME) is increasingly recognized. Both promoting as well as suppressing effects on anti-tumor immunity have been reported in response to rectal cancer (chemo-)radiotherapy and various targets for combination therapies are under investigation. A literature review was conducted searching the PubMed database for evidence regarding the pleiotropic effects of (chemo-)radiotherapy on the rectal cancer TIME, including alterations in cytokine levels, immune cell populations and activity as well as changes in immune checkpoint proteins. Radiotherapy can induce immune-stimulating and -suppressive alterations, potentially mediating radioresistance. The response is influenced by treatment modalities, including the dosage administered and the highly individual intrinsic pre-treatment immune status. Directly addressing the main immune cells of the TME, this review aims to highlight therapeutical implications since efficient rectal cancer treatment relies on personalized strategies combining conventional therapies with immune-modulating approaches, such as immune checkpoint inhibitors.

Novel Tumor Organoid-Based Mouse Model to Study Image Guided Radiation Therapy of Rectal Cancer After Noninvasive and Precise Endoscopic Implantation

PurposePreoperative (neoadjuvant) radiation therapy (RT) is an essential part of multimodal rectal cancer therapy. Recently, total neoadjuvant therapy (TNT) which combines simultaneous radio-chemotherapy with additional courses of chemotherapy (CTx) has emerged as an effective approach. TNT achieves a pathological complete remission in approximately 30% of resected patients, opening avenues for treatment strategies that avoid radical organ resection. Furthermore, recent studies have demonstrated that anti-PD-1 immunotherapy (IT) can induce clinical complete responses in patients with specific genetic alterations. Overall, there is significant potential to enhance outcomes through intensifying, personalizing, and de-escalating treatment approaches. However, the heterogeneous response rates to RT or TNT and strategies to sensitize patients without specific genetic changes to IT remain poorly understood. Materials and MethodsWe developed a novel orthotopic mouse model of rectal cancer which is based on precisely defined endoscopic injections of tumor organoids that reflect tumor heterogeneity. Subsequently, we employed endoscopic- and computed tomography-guided RT, and validated rectal tumor growth and response rates to therapy using small animal magnetic resonance imaging and endoscopic follow-up. ResultsRectal tumor formation was successfully induced in all mice following two organoid injections. Clinically relevant RT regimens with 5 × 5 Gy significantly delayed clinical signs of tumor progression and significantly improved survival. Consistent with human disease, rectal tumor progression correlated with the development of liver and lung metastases. Notably, longterm survivors after RT showed no evidence of tumor recurrence, as demonstrated by in vivo radiological tumor staging and histopathological examination. ConclusionsOur novel mouse model combines orthotopic tumor growth via non-invasive and precise rectal organoid injection and small animal RT. This model holds significant promise for investigating the impact of tumor cell-intrinsic aspects, genetic alterations of the host, or exogenous factors (e.g., nutrition or microbiota) on RT outcomes. Furthermore, it allows for the exploration of combination therapies involving CTx, IT or novel targeted therapies.