Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer.

BACKGROUND: Mismatch repair-deficient (dMMR) tumors can be found in 10 to 15% of patients with nonmetastatic colon cancer. In these patients, the efficacy of chemotherapy is limited. The use of neoadjuvant immunotherapy has shown promising results, but data from studies of this approach are limited. METHODS: We conducted a phase 2 study in which patients with nonmetastatic, locally advanced, previously untreated dMMR colon cancer were treated with neoadjuvant nivolumab plus ipilimumab. The two primary end points were safety, defined by timely surgery (i.e., ≤2-week delay of planned surgery owing to treatment-related toxic events), and 3-year disease-free survival. Secondary end points included pathological response and results of genomic analyses. RESULTS: Of 115 enrolled patients, 113 (98%; 97.5% confidence interval [CI], 93 to 100) underwent timely surgery; 2 patients had surgery delayed by more than 2 weeks. Grade 3 or 4 immune-related adverse events occurred in 5 patients (4%), and none of the patients discontinued treatment because of adverse events. Among the 111 patients included in the efficacy analysis, a pathological response was observed in 109 (98%; 95% CI, 94 to 100), including 105 (95%) with a major pathological response (defined as ≤10% residual viable tumor) and 75 (68%) with a pathological complete response (0% residual viable tumor). With a median follow-up of 26 months (range, 9 to 65), no patients have had recurrence of disease. CONCLUSIONS: In patients with locally advanced dMMR colon cancer, neoadjuvant nivolumab plus ipilimumab had an acceptable safety profile and led to a pathological response in a high proportion of patients. (Funded by Bristol Myers Squibb; NICHE-2 ClinicalTrials.gov number, NCT03026140.).

Trends in epidemiology and primary treatment of anal squamous cell carcinoma in the Netherlands (1990-2021).

A rapid increase in the incidence of anal squamous cell carcinoma (SCC) was reported in several countries over the past decades. This study assessed trends in epidemiology and primary treatment over a 32-year period (1990-2021) using the Netherlands Cancer Registry. The study population included 4273 patients, 44.2% male and 55.8% female (median age 63 years). The age-standardised incidence rate (European Standardised Rate, ESR) increased from 0.5 to 1.6 per 100,000, which entailed an average annual percentage change (AAPC) of 5.0% (95% confidence interval [CI]: 4.5%-5.8%). While incidence among females increased continuously over the total period (AAPC 4.9%; 95%CI: 4.4%-5.6%), to 1.8 per 100,000 ESR in 2021, incidence among males increased until 2016 (annual percentage change [APC] of 6.3%; 95%CI: 5.6%-10.7%), after which it seemed to stabilise (APC -2.1%; 95%CI: -16.8%-4.5%). Significant trends were also observed in distribution of age, tumour stage and primary treatment modalities. Five-year relative survival (RS) was estimated using the Pohar-Perme estimator, and this improved from 56.1% in 1990-1997 (95%CI: 49.3%-62.4%) to 67.9% in 2014-2021 (95%CI: 64.7%-70.9%), but remained poor for stage IV disease. Evaluation through a multivariable Poisson regression model demonstrated diagnosis in the most recent period to be independently associated with better RS, in addition to female sex, younger age, early disease stage and any treatment. In conclusion, the rising incidence of anal SCC seems to decline in males, but not in females, and advances in diagnostics and therapeutic management have likely contributed to improved prognosis.

Whole-body MRI with diffusion-weighted imaging as an adjunct to18 F-fluorodeoxyglucose positron emission tomography and CT in patients with suspected recurrent colorectal cancer.

AIM: The aim was to explore how findings of whole-body MRI including diffusion-weighted imaging (DW-MRI) compared to the routine diagnostic workup with CT and/or 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with suspected recurrent colorectal cancer (CRC). METHOD: This was an exploratory retrospective analysis of 55 patients with a clinical suspicion of recurrent CRC who underwent DW-MRI following CT and/or FDG-PET/CT. Two readers in consensus interpreted all clinical imaging reports and converted each described lesion into a confidence score (1 = definitely benign to 5 = definitely malignant). DW-MRI findings were compared to the most recent previous CT or PET/CT. Any discrepant or additional DW-MRI findings were documented and compared with histology and/or clinical follow-up (if available). RESULTS: Whole-body MRI including diffusion-weighted imaging (DW-MRI) resulted in discrepant/additional findings in 26/55 (47%) cases; 23/37 (62%) compared to previous CT and 3/18 (17%) compared to previous PET/CT. These included 10 cases where DW-MRI converted previously inconclusive CT (n = 8) or PET/CT (n = 2) findings into a conclusive diagnosis, one where it contradicted a previous CT diagnosis of recurrence, five where DW-MRI diagnosed recurrent disease not previously reported on CT and 10 cases where DW-MRI detected additional lesions compared to CT (n = 9) or PET/CT (n = 1). Eighty-eight per cent of cases with discrepant/additional findings concerned patients with recurrent/metachronous peritoneal metastases. In total, DW-MRI resulted in 42 discrepant/additional lesions; the DW-MRI diagnosis was correct in 76% of these lesions and incorrect (false positive) in 7%. In the remaining 17%, no standard of reference was available. CONCLUSIONS: This explorative study suggests that DW-MRI may be of added value to patients with a clinical suspicion for recurrent CRC, in particular to identify patients with peritoneal metastases. DW-MRI mainly has potential as a 'problem-solver' in patients with inconclusive or negative findings on previous imaging (in particular CT) and to detect additional disease sites in patients already diagnosed with recurrent disease.

Better stoma care using the Stoma App: does it help? A first randomized double-blind clinical trial on the effect of mobile healthcare on quality of life in stoma patients.

BACKGROUND: Receiving a stoma significantly impacts patients' quality of life. Coping with this new situation can be difficult, which may result in a variety of physical and psychosocial problems. It is essential to provide adequate guidance to help patients cope with their stoma, as this positively influences self-efficacy in return. Higher self-efficacy reduces psychosocial problems increasing patient's quality of life. This study investigates whether a new mobile application, the Stoma App, improves quality of life. And if personalized guidance, timed support, and peer contact offered as an in-app surplus makes a difference. METHODS: A double-blind, randomized controlled trial was conducted between March 2021 and April 2023. Patients aged > 18 years undergoing ileostomy or colostomy surgery, in possession of a compatible smartphone were included. The intervention group received the full version of the app containing personalized and time guidance, peer support, and generic (non-personalized) stoma-related information. The control group received a restricted version with only generic information. Primary outcome was stoma quality of life. Secondary outcomes included psychological adaption, complications, re-admittance, reoperations, and length of hospital stay. RESULTS: The intervention version of the app was used by 96 patients and the control version by 112 patients. After correction for confounding, the intervention group reported a significant 3.1-point improvement in stoma-related quality of life one month postoperatively (p = 0.038). On secondary outcomes, no significant improvements could be retrieved of the intervention group. CONCLUSION: The Stoma App improves the quality of life of stoma patients. Peer support and personalized guidance are of significant importance in building self-efficacy. It is to be recommended to implement Stoma app-freely available software qualifying as a medical device-in standard stoma care pathways for the benefits of both patients and healthcare providers.

Imaging Photoplethysmography for Noninvasive Anastomotic Perfusion Assessment in Intestinal Surgery.

INTRODUCTION: Anastomotic leakage after gastrointestinal surgery has a high impact on patient's quality of life and its origin is associated with inadequate perfusion. Imaging photoplethysmography (iPPG) is a noninvasive imaging technique that measures blood-volume changes in the microvascular tissue bed and detects changes in tissue perfusion. MATERIALS AND METHODS: Intraoperative iPPG imaging was performed in 29 patients undergoing an open segment resection of the small intestine or colon. During each surgery, imaging was performed on fully perfused (true positives) and ischemic intestines (true negatives) and the anastomosis (unknowns). Imaging consisted of a 30-s video from which perfusion maps were extracted, providing detailed information about blood flow within the intestine microvasculature. To detect the predictive capabilities of iPPG, true positive and true negative perfusion conditions were used to develop two different perfusion classification methods. RESULTS: iPPG-derived perfusion parameters were highly correlated with perfusion-perfused or ischemic-in intestinal tissues. A perfusion confidence map distinguished perfused and ischemic intestinal tissues with 96% sensitivity and 86% specificity. Anastomosis images were scored as adequately perfused in 86% of cases and 14% inconclusive. The cubic-Support Vector Machine achieved 90.9% accuracy and an area under the curve of 96%. No anastomosis-related postoperative complications were encountered in this study. CONCLUSIONS: This study shows that noninvasive intraoperative iPPG is suitable for the objective assessment of small intestine and colon anastomotic perfusion. In addition, two perfusion classification methods were developed, providing the first step in an intestinal perfusion prediction model.

Selected stage IV rectal cancer patients managed by the watch-and-wait approach after pelvic radiotherapy: a good alternative to total mesorectal excision surgery?

AIM: The aim of this study was to assess the clinical and oncological outcome of a selected group of stage IV rectal cancer patients managed by the watch-and-wait approach following a (near-)complete response of the primary rectal tumour after radiotherapy. METHOD: Patients registered in the Dutch watch-and-wait registry since 2004 were selected when diagnosed with synchronous stage IV rectal cancer. Data on patient characteristics, treatment details, follow-up and survival were collected. The 2-year local regrowth rate, organ-preservation rate, colostomy-free rate, metastatic progression-free rate and 2- and 5-year overall survival were analysed. RESULTS: After a median follow-up period of 35 months, local regrowth was observed in 17 patients (40.5%). Nine patients underwent subsequent total mesorectal excision, resulting in a permanent colostomy in four patients. The 2-year local regrowth rate was 39.9%, the 2-year organ-preservation rate was 77.1%, the 2-year colostomy-free rate was 88.1%, and the 2-year metastatic progression-free rate was 46.7%. The 2- and 5-year overall survival rates were 92.0% and 67.5%. CONCLUSION: The watch-and-wait approach can be considered as an alternative to total mesorectal excision in a selected group of stage IV rectal cancer patients with a (near-)complete response following pelvic radiotherapy. Despite a relatively high regrowth rate, total mesorectal excision and a permanent colostomy can be avoided in the majority of these patients.

Challenges and controversies patients and (health care) professionals experience in managing vaginal, vulvar, penile or anal cancer: The SILENCE study.

OBJECTIVE: Patients with vaginal, vulvar, penile or anal cancer experience deteriorated psychosocial functioning and decreased Quality of Life (QoL). The aims of this study were to explore (1) the challenges and controversies patients experience in managing vaginal, vulvar, penile or anal cancer; their unmet needs; and how this affects their psychosocial functioning and (2) the gaps health care professionals (HCPs) experience in providing psychosocial support and potential improvements in care. METHODS: Semi-structured interviews with patients with vaginal, vulvar, penile or anal cancer and with HCPs were conducted. All interviews were transcribed verbatim and thematically analysed. RESULTS: Fourteen patients (86% female; mean age 55.5) and 12 HCPs (75% female; mean age 46.4) participated. Four themes were identified: (1) recognisable symptoms but unfamiliar diagnosis, (2) 'double hit' has severe impact on psychosocial functioning, (3) personal and tailored information is important but not guaranteed and (4) all-encompassing care to improve psychosocial functioning and QoL. CONCLUSION: Patients with vaginal, vulvar, penile or anal cancer encounter a lack of awareness and knowledge about their rare cancer type, difficulties regarding communication and long-term changes in body image and sexuality. Awareness of symptoms should be raised and psychosocial care should be offered on a structural basis.

Yield of Screening for COVID-19 in Asymptomatic Patients Before Elective or Emergency Surgery Using Chest CT and RT-PCR (SCOUT): Multicenter Study.

OBJECTIVE: To determine the yield of preoperative screening for COVID-19 with chest CT and RT-PCR in patients without COVID-19 symptoms. SUMMARY OF BACKGROUND DATA: Many centers are currently screening surgical patients for COVID-19 using either chest CT, RT-PCR or both, due to the risk for worsened surgical outcomes and nosocomial spread. The optimal design and yield of such a strategy are currently unknown. METHODS: This multicenter study included consecutive adult patients without COVID-19 symptoms who underwent preoperative screening using chest CT and RT-PCR before elective or emergency surgery under general anesthesia. RESULTS: A total of 2093 patients without COVID-19 symptoms were included in 14 participating centers; 1224 were screened by CT and RT-PCR and 869 by chest CT only. The positive yield of screening using a combination of chest CT and RT-PCR was 1.5% [95% confidence interval (CI): 0.8-2.1]. Individual yields were 0.7% (95% CI: 0.2-1.1) for chest CT and 1.1% (95% CI: 0.6-1.7) for RT-PCR; the incremental yield of chest CT was 0.4%. In relation to COVID-19 community prevalence, up to ∼6% positive RT-PCR was found for a daily hospital admission rate >1.5 per 100,000 inhabitants, and around 1.0% for lower prevalence. CONCLUSIONS: One in every 100 patients without COVID-19 symptoms tested positive for SARS-CoV-2 with RT-PCR; this yield increased in conjunction with community prevalence. The added value of chest CT was limited. Preoperative screening allowed us to take adequate precautions for SARS-CoV-2 positive patients in a surgical population, whereas negative patients needed only routine procedures.

Implementation of a New High-Volume Circular Stapler in Stapled Anopexy for Hemorrhoidal Disease: Is Patient's Short-Term Outcome Affected by a Higher Volume of Resected Tissue?

BACKGROUND: Stapled anopexy is a safe technique for the treatment of hemorrhoids but carries a higher risk of recurrence, which might be caused due to the limited volume of resected tissue. In this study, we investigated the introduction of a high-volume circular stapling device; in particular whether an increased amount of resected tissue could affect patients' short-term postoperative outcome. METHODS: Between 2011 and 2015, stapled anopexy was performed for hemorrhoids and/or anal prolapse in 141 patients (n = 25 conventional PPH-3©-stapler versus n = 116 high-volume CHEX©-stapler). In this prospectively collected dataset, operation details and short-term postoperative outcome were compared. RESULTS: With the high-volume stapler, a significantly higher amount of tissue was resected: 9.8 g (range 6.2-11.4) vs. 6.4 g (range 4.9-8.8) with the conventional stapler, p < 0.01. Postoperative short-term outcome did not differ in terms of readmission and complication rates. In all 5 patients who underwent a redo operation for residual hemorrhoids or prolapse, the high-volume stapler was used in the primary operation. CONCLUSION: A high-volume stapling device for stapled anopexy was introduced safely with a significantly higher amount of resected tissue without a worse short-term outcome. However, it remains unclear whether higher stapling volumes may lead to improved long-term outcome with less reinterventions.

Sarcopenia/Muscle Mass is not a Prognostic Factor for Short- and Long-Term Outcome After Esophagectomy for Cancer.

BACKGROUND: Recent studies have suggested that sarcopenia is a prognostic risk indicator of postoperative complications and predicts survival in cancer patients. The aim of this study is to investigate whether sarcopenia is associated with postoperative short-term outcome (morbidity and mortality) and long-term survival in patients undergoing esophagectomy for cancer after neoadjuvant chemoradiotherapy. METHODS: All patients who underwent neoadjuvant chemoradiotherapy followed by esophagectomy for cancer, and of whom an adequate CT scan was available, were included in the current study. The presence of sarcopenia was defined by CT imaging using cut-off values of the total cross-sectional muscle tissue measured transversely at the third lumbar level. RESULTS: A total number of 120 patients were eligible for analysis. Almost half of the patients (N = 54, 45 %) were classified as having sarcopenia; 24 sarcopenic patients (44 %) had overweight and 5 sarcopenic patients (9 %) were obese. Overall morbidity and mortality rate did not differ significantly between sarcopenic and non-sarcopenic patients, nor did long-term overall or disease-free survival. Also sarcopenic obesity was not associated with worse outcome. CONCLUSION: The presence of sarcopenia was not associated with a negative short- and long-term outcome in this selected group of esophageal cancer patients after neoadjuvant chemoradiotherapy followed by esophagectomy.

The use of negative-pressure wound therapy in pilonidal sinus disease: a randomized controlled trial comparing negative-pressure wound therapy versus standard open wound care after surgical excision.

BACKGROUND: Pilonidal sinus disease is associated with significant morbidity after surgical treatment with regard to wound healing. Recent case studies suggested that negative-pressure wound therapy as primary treatment following surgical excision may shorten the duration of wound healing. OBJECTIVE: The purpose of this randomized controlled trial was to evaluate the role of vacuum therapy in pilonidal sinus disease: negative-pressure wound therapy versus standard open wound care after surgical excision. METHODS: Patients were randomly assigned to either negative-pressure wound therapy for 2 weeks or standard open wound healing. The primary end point of the study was the time to complete wound healing. Secondary end points were visual analog scale score, wound size ratio at day 14 (ie, wound healing rate), time to resume daily activities, and recurrence within 6 months after wound closure. RESULTS: Forty-nine patients were included in the study: 24 patients were treated with vacuum therapy, and 25 patients underwent standard open wound care. Complete wound healing was achieved at a median of 84 days in the vacuum therapy group versus 93 days in control patients (p = 0.44). The wound size ratio was significantly lower in the vacuum therapy group (0.30 versus 0.57, p = 0.02), ie, higher wound healing rate in the first 2 weeks. There was no difference in visual analog scale scores and disease recurrence between both groups. The time to resume full daily activities after surgery was 27 days in the patients undergoing vacuum therapy and 29 days in the control patients (p = 0.92). LIMITATIONS: This study is limited by the small number of patients, the lack of blinding to patients and doctors, and the absence of patient quality-of-life evaluation. CONCLUSION: It is feasible to apply vacuum therapy in the treatment of pilonidal sinus disease, and it has a positive effect on wound size reduction in the first 2 weeks. However, there is no difference in time to complete wound healing and time to resume daily life activities.

Preoperative assessment of tumor location and station-specific lymph node status in patients with adenocarcinoma of the gastroesophageal junction.

BACKGROUND: In esophageal cancer patients preoperative staging will determine the type of surgical procedure and use of neoadjuvant therapy. Tumor location and lymph node status play a pivotal role in this tailored strategy. The aim of the present study was to prospectively evaluate the accuracy of preoperative assessment of tumor location according to the Siewert classification and lymph node status per station with endoscopy/endoscopic ultrasound (EUS) and computed tomography (CT). METHODS: In 50 esophagectomy patients with adenocarcinoma of the gastroesophageal junction (GEJ), tumor location according to Siewert and N-stage per nodal station as determined preoperatively by endoscopy/EUS and CT were compared with the histopathologic findings in the resection specimen. RESULTS: Overall accuracy in predicting tumor location according to the Siewert classification was 70 % for endoscopy/EUS and 72 % for CT. Preoperative data could not be compared with the pathologic assessment in 11 patients (22 %), as large tumors obscured the landmark of the gastric folds. The overall accuracy for predicting the N-stage in 250 lymph node stations was 66 % for EUS and 68 % for CT. The accuracy was good for those stations located high in the thorax, but poor for celiac trunk nodes. CONCLUSIONS: Given the frequent discrepancy between the endoscopic and pathologic location of the GEJ and the common problem of advanced tumors obscuring the landmarks used in the assessment of the Siewert classification, its usefulness is limited. The overall accuracy for EUS and CT in predicting the N-stage per station was moderate.

Validated Pretreatment Prediction Models for Response to Neoadjuvant Therapy in Patients with Rectal Cancer: A Systematic Review and Critical Appraisal.

Pretreatment response prediction is crucial to select those patients with rectal cancer who will benefit from organ preservation strategies following (intensified) neoadjuvant therapy and to avoid unnecessary toxicity in those who will not. The combination of individual predictors in multivariable prediction models might improve predictive accuracy. The aim of this systematic review was to summarize and critically appraise validated pretreatment prediction models (other than radiomics-based models or image-based deep learning models) for response to neoadjuvant therapy in patients with rectal cancer and provide evidence-based recommendations for future research. MEDLINE via Ovid, Embase.com, and Scopus were searched for eligible studies published up to November 2022. A total of 5006 studies were screened and 16 were included for data extraction and risk of bias assessment using Prediction model Risk Of Bias Assessment Tool (PROBAST). All selected models were unique and grouped into five predictor categories: clinical, combined, genetics, metabolites, and pathology. Studies generally included patients with intermediate or advanced tumor stages who were treated with neoadjuvant chemoradiotherapy. Evaluated outcomes were pathological complete response and pathological tumor response. All studies were considered to have a high risk of bias and none of the models were externally validated in an independent study. Discriminative performances, estimated with the area under the curve (AUC), ranged per predictor category from 0.60 to 0.70 (clinical), 0.78 to 0.81 (combined), 0.66 to 0.91 (genetics), 0.54 to 0.80 (metabolites), and 0.71 to 0.91 (pathology). Model calibration outcomes were reported in five studies. Two collagen feature-based models showed the best predictive performance (AUCs 0.83-0.91 and good calibration). In conclusion, some pretreatment models for response prediction in rectal cancer show encouraging predictive potential but, given the high risk of bias in these studies, their value should be evaluated in future, well-designed studies.

Long-term Quality of Life and Functional Outcome of Patients With Rectal Cancer Following a Watch-and-Wait Approach.

Importance: A watch-and-wait approach for patients with rectal cancer and a clinical complete response after neoadjuvant chemoradiotherapy or radiotherapy is associated with better quality of life and functional outcome. Nevertheless, prospective data on both parameters are scarce. Objective: To prospectively evaluate quality of life and functional outcome, including bowel, urinary, and sexual function, of patients following a watch-and-wait approach. Design, Setting, and Participants: A total of 278 patients with rectal cancer and a clinical complete response or near-complete response after neoadjuvant chemoradiotherapy or radiotherapy were included in 2 prospective cohort studies: a single-center study (March 2014 to October 2017) and an ongoing multicenter study (from September 2017). Patients were observed by a watch-and-wait approach. Additional local excision or total mesorectal excision was performed for residual disease or regrowth. Data were analyzed between April 1, 2021, and August 27, 2021, for patients with a minimum follow-up of 24 months. Main Outcomes and Measures: Quality of life was evaluated with the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-C30 (EORTC-QLQ-C30), EORTC-QLQ-CR38, or EORTC-QLQ-CR29 and 36-Item Short-Form Health Survey. The score for the questionnaires and 36-Item Short-Form Health Survey ranges from 0 to 100. For some scales, a high score indicates a high level of functioning, and for others it indicates a high level of complaints and symptomatology. Functional outcome was assessed by the Low Anterior Resection Syndrome score, Vaizey incontinence score, International Prostate Symptom Score, International Index of Erectile Function, and Female Sexual Function Index. Results: Of 278 patients included, 187 were male (67%), and the median age was 66 years (range, 34-85 years). In the first 24 months, 221 patients (80%) were observed by a watch-and-wait approach without requiring surgery, 18 patients (6%) underwent additional local excision, and 39 patients (14%) underwent total mesorectal excision. In general, patients observed by a watch-and-wait approach reported good quality of life, with limited variation over time. At 3 months, 56 of 221 patients (25.3%) reported major bowel dysfunction; at 12 months, 53 patients (24.0%) reported it; and at 24 months, 55 patients (24.9%) reported it. At 24 months, 48 of 151 male patients (31.8%) reported severe erectile dysfunction. For female patients, sexual satisfaction and overall sexual function decreased during follow-up. Patients who underwent local excision reported more major bowel dysfunction (10 of 18 patients [55.6%]) compared with those without additional surgery. Quality-of-life scores, however, were comparable. After total mesorectal excision, patients scored significantly worse on several quality-of-life subscales. Conclusions and Relevance: Results of this study suggest that patients with rectal cancer who were observed by a watch-and-wait approach had good quality of life, with some patients reporting bowel and sexual dysfunction. Quality of life and functional outcome deteriorated when patients required surgery. These data will be useful in daily care to counsel patients on what to expect from a watch-and-wait approach.

MRI anatomy of the rectum: key concepts important for rectal cancer staging and treatment planning.

A good understanding of the MRI anatomy of the rectum and its surroundings is pivotal to ensure high-quality diagnostic evaluation and reporting of rectal cancer. With this pictorial review, we aim to provide an image-based overview of key anatomical concepts essential for treatment planning, response evaluation and post-operative assessment. These concepts include the cross-sectional anatomy of the rectal wall in relation to T-staging; differences in staging and treatment between anal and rectal cancer; landmarks used to define the upper and lower boundaries of the rectum; the anatomy of the pelvic floor and anal canal, the mesorectal fascia, peritoneum and peritoneal reflection; and guides to help discern different pelvic lymph node stations on MRI to properly stage regional and non-regional rectal lymph node metastases. Finally, this review will highlight key aspects of post-treatment anatomy, including the assessment of radiation-induced changes and the evaluation of the post-operative pelvis after different surgical resection and reconstruction techniques.

Size and depth of residual tumor after neoadjuvant chemoradiotherapy in rectal cancer - implications for the development of new imaging modalities for response assessment.

With the shift towards organ preserving treatment strategies in rectal cancer it has become increasingly important to accurately discriminate between a complete and good clinical response after neoadjuvant chemoradiotherapy (CRT). Standard of care imaging techniques such as CT and MRI are well equipped for initial staging of rectal tumors, but discrimination between a good clinical and complete response remains difficult due to their limited ability to detect small residual vital tumor fragments. To identify new promising imaging techniques that could fill this gap, it is crucial to know the size and invasion depth of residual vital tumor tissue since this determines the requirements with regard to the resolution and imaging depth of potential new optical imaging techniques. We analyzed 198 pathology slides from 30 rectal cancer patients with a Mandard tumor regression grade 2 or 3 after CRT that underwent surgery. For each patient we determined response pattern, size of the largest vital tumor fragment or bulk and the shortest distance from the vital tumor to the luminal surface. The response pattern was shrinkage in 14 patients and fragmentation in 16 patients. For both groups combined, the largest vital tumor fragment per patient was smaller than 1mm for 38% of patients, below 0.2mm for 12% of patients and for one patient as small as 0.06mm. For 29% of patients the vital tumor remnant was present within the first 0.01mm from the luminal surface and for 87% within 0.5mm. Our results explain why it is difficult to differentiate between a good clinical and complete response in rectal cancer patients using endoscopy and MRI, since in many patients submillimeter tumor fragments remain below the luminal surface. To detect residual vital tumor tissue in all patients included in this study a technique with a spatial resolution of 0.06mm and an imaging depth of 8.9mm would have been required. Optical imaging techniques offer the possibility of detecting majority of these cases due to the potential of both high-resolution imaging and enhanced contrast between tissue types. These techniques could thus serve as a complimentary tool to conventional methods for rectal cancer response assessment.

Sense and non-sense of imaging in the era of organ preservation for rectal cancer.

This review summarizes the current applications and benefits of imaging modalities for organ preservation in the treatment of rectal cancer. The concept of organ preservation in the treatment of rectal cancer has revolutionized the way rectal cancer is managed. Initially, organ preservation was limited to patients with locally advanced rectal cancer who needed neoadjuvant therapy to reduce tumor size before surgery and achieved complete response. However, neoadjuvant therapy is now increasingly utilized for smaller and less aggressive tumors to achieve primary organ preservation. Additionally, more intensive neoadjuvant strategies are employed to improve complete response rates and increase the chances of successful organ preservation. The selection of patients for organ preservation is a critical component of treatment, and imaging techniques such as digital rectal exam, endoscopy, and MRI are commonly used for this purpose. In this review, we provide an overview of what imaging modalities should be chosen and how they can aid in the selection and follow-up of patients undergoing organ-preserving strategies.

Correction: Groen et al. Use of Image-Guided Surgical Navigation during Resection of Locally Recurrent Rectal Cancer. Life 2022, 12, 645.

The authors wish to make the following corrections to this paper [...].

Optimisation of Organ Preservation treatment strategies in patients with rectal cancer with a good clinical response after neoadjuvant (chemo)radiotherapy: Additional contact X-ray brachytherapy versus eXtending the observation period and local excision (OPAXX) - protocol for two multicentre, parallel, single-arm, phase II studies.

INTRODUCTION: Standard treatment for patients with intermediate or locally advanced rectal cancer is (chemo)radiotherapy followed by total mesorectal excision (TME) surgery. In recent years, organ preservation aiming at improving quality of life has been explored. Patients with a complete clinical response to (chemo)radiotherapy can be managed safely with a watch-and-wait approach. However, the optimal organ-preserving treatment strategy for patients with a good, but not complete clinical response remains unclear. The aim of the OPAXX study is to determine the rate of organ preservation that can be achieved in patients with rectal cancer with a good clinical response after neoadjuvant (chemo)radiotherapy by additional local treatment options. METHODS AND ANALYSIS: The OPAXX study is a Dutch multicentre study that investigates the efficacy of two additional local treatments aiming at organ preservation in patients with a good, but not complete response to neoadjuvant treatment (ie near-complete response or a small residual tumour mass <3 cm). The sample size will be 168 patients in total. Patients will be randomised (1:1) between two parallel single-arm phase II studies: study arm 1 involves additional contact X-ray brachytherapy (an intraluminal radiation boost), while in study arm 2 the observation period is extended followed by a second response evaluation and optional transanal local excision. The primary endpoint of the study is the rate of successful organ preservation at 1 year following randomisation. Secondary endpoints include toxicity, morbidity, oncological and functional outcomes at 1 and 2 years of follow-up. Finally, an observational cohort study for patients who are not eligible for randomisation is conducted. ETHICS AND DISSEMINATION: The trial protocol has been approved by the medical ethics committee of the Netherlands Cancer Institute (METC20.1276/M20PAX). Informed consent will be obtained from all participants. The trial results will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05772923.

Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial.

INTRODUCTION: Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4-8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT. METHODS AND ANALYSIS: The preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction. ETHICS AND DISSEMINATION: The trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: WHO International Clinical Trials Registry (NL8997; https://trialsearch.who.int).