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.).

Association of Lateral Pelvic Lymph Nodes with Disease Recurrence and Organ Preservation in Patients with Distal Rectal Adenocarcinoma Treated with Total Neoadjuvant Therapy.

OBJECTIVE: Assess the significance of enlarged lateral lymph nodes (LLN) for disease recurrence, metastasis, and organ preservation in patients with rectal cancer. BACKGROUND: Optimal treatment of rectal adenocarcinoma involving LLN is subject to debate. METHODS: A post hoc analysis of the OPRA trial, a multicenter study of patients with rectal cancer treated with total neoadjuvant therapy (TNT) followed by total mesorectal excision or watch-and-wait management. We analyzed the association of visible LLN (LLN+), LLN≥7 mm (short axis) on baseline MRI, and LLN≥4 mm on restaging MRI with recurrence, metastasis, and rectum preservation. RESULTS: At baseline, 57 out of 324 (18%) patients had LLN+. In 30 (53%) of 57 patients with LLN+ on baseline MRI, the LLN disappeared after TNT. Disease recurrence in LLN was rare (3.5% of patients with LLN+ and 0.4% of patients with LLN-). All patients with recurrence in LLN also had distant metastasis. The rate of organ preservation was significantly lower in patients with LLN≥4 mm on restaging MRI (P=0.013). We found no significant differences in rates of local recurrence or metastasis between patients with LLN+ vs. LLN- and in patients with LLN≥7 vs.<7 mm on baseline MRI. LLN dissection was performed in 3 patients; 2 of them died of distant metastasis. CONCLUSIONS: LLN involvement is not associated with disease recurrence or metastasis, but persistence of LLN≥4 mm after TNT is negatively associated with rectum preservation in patients with locally advanced rectal cancer treated with TNT. Dissection of lateral nodes likely benefits few patients.

Prevention of Seroma Formation and Its Sequelae After Axillary Lymph Node Dissection: An Up-to-Date Systematic Review and Guideline for Surgeons.

INTRODUCTION: Seroma formation after axillary lymph node dissection (ALND) remains a troublesome complication with significant morbidity. Numerous studies have tried to identify techniques to prevent seroma formation. The aim of this systematic review and network meta-analysis is to use available literature to identify the best intervention for prevention of seroma after standalone ALND. METHODS: A literature search was performed for all comparative articles regarding seroma formation in patients undergoing a standalone ALND or ALND with breast-conserving surgery in the last 25 years. Data regarding seroma formation, clinically significant seroma (CSS), surgical site infections (SSI), and hematomas were collected. The network meta-analysis was performed using a random effects model and the level of inconsistency was evaluated using the Bucher method. RESULTS: A total of 19 articles with 1962 patients were included. Ten different techniques to prevent seroma formation were described. When combining direct and indirect comparisons, axillary drainage until output is less than 50 ml per 24 h for two consecutive days results in significantly less CSS. The use of energy sealing devices, padding, tissue glue, or patches did not significantly reduce the incidence of CSS. When comparing the different techniques with regard to SSIs, no statistically significant differences were seen. CONCLUSIONS: To prevent CSS after ALND, axillary drainage is the most valuable and scientifically proven measure. On the basis of the results of this systematic review with network meta-analysis, removing the drain when output is < 50 ml per 24 h for two consecutive days irrespective of duration seems best. Since drainage policies vary widely, an evidence-based guideline is needed.

Outcomes and potential impact of a virtual hands-on training program on MRI staging confidence and performance in rectal cancer.

OBJECTIVES: To explore the potential impact of a dedicated virtual training course on MRI staging confidence and performance in rectal cancer. METHODS: Forty-two radiologists completed a stepwise virtual training course on rectal cancer MRI staging composed of a pre-course (baseline) test with 7 test cases (5 staging, 2 restaging), a 1-day online workshop, 1 month of individual case readings (n = 70 cases with online feedback), a live online feedback session supervised by two expert faculty members, and a post-course test. The ESGAR structured reporting templates for (re)staging were used throughout the course. Results of the pre-course and post-course test were compared in terms of group interobserver agreement (Krippendorf's alpha), staging confidence (perceived staging difficulty), and diagnostic accuracy (using an expert reference standard). RESULTS: Though results were largely not statistically significant, the majority of staging variables showed a mild increase in diagnostic accuracy after the course, ranging between + 2% and + 17%. A similar trend was observed for IOA which improved for nearly all variables when comparing the pre- and post-course. There was a significant decrease in the perceived difficulty level (p = 0.03), indicating an improved diagnostic confidence after completion of the course. CONCLUSIONS: Though exploratory in nature, our study results suggest that use of a dedicated virtual training course and web platform has potential to enhance staging performance, confidence, and interobserver agreement to assess rectal cancer on MRI virtual training and could thus be a good alternative (or addition) to in-person training. CLINICAL RELEVANCE STATEMENT: Rectal cancer MRI reporting quality is highly dependent on radiologists' expertise, stressing the need for dedicated training/teaching. This study shows promising results for a virtual web-based training program, which could be a good alternative (or addition) to in-person training. KEY POINTS: • Rectal cancer MRI reporting quality is highly dependent on radiologists' expertise, stressing the need for dedicated training and teaching. • Using a dedicated virtual training course and web-based platform, encouraging first results were achieved to improve staging accuracy, diagnostic confidence, and interobserver agreement. • These exploratory results suggest that virtual training could thus be a good alternative (or addition) to in-person training.

Imaging in pelvic exenteration-a multidisciplinary practice guide from the ESGAR-SAR-ESUR-PelvEx collaborative group.

Pelvic exenteration (PE) is a radical surgical approach designed for the curative treatment of advanced pelvic malignancies, requiring en-bloc resection of multiple pelvic organs. While the procedure is radical, it has shown promise in enhancing long-term survival and is now comparable in surgical mortality to elective resections for primary pelvic cancers. Imaging plays a crucial role in preoperative planning, with MRI, CT, and PET/CT being pivotal in assessing the extent of cancer and formulating a surgical roadmap. This paper presents clinical practice guidelines for imaging in the context of PE, developed jointly by ESGAR, SAR, ESUR, and the PelvEx Collaborative. These guidelines aim to standardize imaging protocols and reporting to improve the preoperative assessment and facilitate decision-making in the multidisciplinary treatment of pelvic cancers. Our recommendations underscore the importance of a multidisciplinary approach and the need for clear and precise imaging reports to optimize patient care. CLINICAL RELEVANCE STATEMENT: Our recommendations underscore the importance of a multidisciplinary approach and the need for clear and precise imaging reports to optimize patient care. KEY POINTS: MRI is mandatory for local staging in pelvic exenteration. Structured reporting (using the template provided in this guide) is recommended. Multidisciplinary review of imaging is critical for surgical planning.

What To Do With Suspected Nodal Regrowth on Magnetic Resonance Imaging During Follow-up in an Organ Preservation Approach for Rectal Cancer?

BACKGROUND: For nodal regrowth in patients with rectal cancer following watch-and-wait standardized protocols on diagnostic procedures and subsequent treatment are lacking. OBJECTIVE: Evaluate the diagnosis and treatment of suspected nodal regrowth following an organ preservation approach. SETTINGS: Patients were included from national and institutional watch-and-wait -databases. DESIGN: Thirty-five rectal cancer patients with suspected nodal regrowth on magnetic resonance imaging were retrospectively identified during watch-and-wait follow-up. PATIENTS: Twenty-seven of 35 patients followed watch-and-wait after neoadjuvant (chemo)radiotherapy and 8/35 followed watch-and-wait schedule after local excision for early rectal cancer. MAIN OUTCOME MEASURES: Diagnostic procedures, treatment and histopathological outcome. RESULTS: Median follow-up was 34 months. Median time from end of (chemo)radiotherapy or local excision to first detection of suspected nodal regrowth on magnetic resonance imaging following watch-and-wait was 9 and 10 months. After first detection, 17 of 35 patients underwent immediate treatment without further diagnostics, of whom 7 also had luminal regrowth. In 18 of 35 patients, additional diagnostic procedures were performed. In 4 of 18 patients, positron emission tomography-computed tomography or endorectal ultrasound-guided biopsy was performed and treatment was initiated based on increased nodal regrowth suspicion. In 14 of 18 patients, MRI was repeated after 8-12 weeks: growth of suspected lymph nodes was the most decisive factor to proceed to treatment. In 8 patients, repeated magnetic resonance imaging was combined with positron emission tomography-computed tomography and/or endorectal ultrasound-guided biopsy: in half of them it contributed to treatment initiation. In total, 34/35 patients were treated: 9 received (re-)irradiation and 33 underwent total mesorectal excision. In 27 of 33 patients, nodal regrowth was pathologically confirmed in the total mesorectal excision-resection specimen; 5 of 6 patients without nodal involvement had pathologically confirmed luminal regrowth. LIMITATIONS: Highly selected study population. CONCLUSIONS: During watch-and-wait follow-up of patients with rectal cancer in an organ preservation strategy, magnetic resonance imaging plays an important role in diagnosis of nodal regrowth. Repeated magnetic resonance imaging after an interval can be helpful in making treatment decisions, and the role of positron emission tomography-computed tomography and endorectal ultrasound-guided biopsy appears limited. See Video Abstract.

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

BACKGROUND: 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. OBJECTIVE: The aim of this study was to reach expert-based consensus on the definition of a clinical near-complete response after (chemo) radiotherapy. DESIGN: 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). SETTING: 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. MAIN OUTCOME MEASURES: The main outcome was to reach consensus (80% or more agreement). RESULTS: 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. LIMITATIONS: 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. CONCLUSIONS: 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. UN CONSENSO INTERNACIONAL BASADO EN EXPERTOS ACERCA DE LA DEFINICIN DE UNA RESPUESTA CLNICA CASI COMPLETA DESPUS DE QUIMIORADIOTERAPIA NEOADYUVANTE CONTRA EL CNCER DE RECTO: 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).

Seroma formation after mastectomy: A systematic review and network meta-analysis of different flap fixation techniques.

Flap fixation is the most promising solution to prevent seroma formation after mastectomy. In this systematic review with network meta-analysis (NMA), three different techniques were compared. The NMA included 25 articles, comprising 3423 patients, and revealed that sutures are superior to tissue glue in preventing clinically significant seroma. In addition, running sutures seemed to be superior to interrupted sutures. An RCT comparing these suture techniques seems necessary, given the quality and nature of existing literature.

Drain-free mastectomy and flap fixation: The interim analysis of a randomized controlled noninferiority trial.

INTRODUCTION: Flap fixation after mastectomy has proven to be one of the most promising solutions to reduce seroma formation. Drain placement remains standard practice in many clinics, even though this may be redundant after flap fixation. METHODS: This is a prospective randomized controlled trial comparing mastectomy and wound closure using flap fixation with or without drain placement. The primary outcome measure was clinically significant seroma (CSS) incidence. The aim of this interim analysis was to assess the assumptions for the sample size calculation and to provide preliminary results. RESULTS: Between July 2020 and January 2023, 112 patients were included. CSS incidence was 9.1% in the drain group and 21% in the no-drain group. In total, 10 patients were lost to follow-up. These numbers are similar to the ones used for the sample size calculation. In the drain group, three patients required interventions for wound complications compared to nine in the no-drain group (odds ratio: 3.612 [95% confidence interval: 0.898-14.537]). CONCLUSION: The sample size calculation seems to be correct and no protocol amendments are necessary. Current preliminary results show no significant differences in CSS incidence. Complete results should be awaited to draw a well-powered conclusion regarding drain policy after mastectomy.

Quality of life and functional outcome of rectal cancer patients: A prospective cohort study.

AIM: In the last decade, the Netherlands has implemented various diagnostic and treatment strategies to enhance rectal cancer outcomes. This study, using data from the Prospective Dutch ColoRectal Cancer (PLCRC) cohort, investigates whether these multidisciplinary advancements have translated into improved health-related quality of life (HRQoL) and functional outcomes for the general Dutch rectal cancer population. METHODS: Patients with Stage I-III rectal cancer enrolled in the PLCRC cohort were included. HRQoL and functional outcomes were assessed 1 and 2 years after diagnosis using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), EORTC QLQ Colorectal Cancer 29 and the Low Anterior Resection Syndrome score. HRQoL and functional outcomes were compared based on year of diagnosis (2014-2019). RESULTS: A total of 1294 patients were included. Two years after diagnosis, patients diagnosed in 2019 (n = 392) had a clinically relevant higher score on physical (8.2, 95% CI 4.1-12.3), role (13.5, 95% CI 7.3-19.7) and social functioning (5.8, 95% CI 0.3-11.2) compared to those diagnosed in 2014 (n = 65). Additionally, patients diagnosed in 2019 experienced less fatigue 2 years after diagnosis compared to those diagnosed in 2014 (-8.6, 95% CI -14.1 to -3.0). The Low Anterior Resection Syndrome score showed no differences. CONCLUSION: The findings of this study suggest that over the past decade rectal cancer patients in the Netherlands have witnessed improvements in HRQoL across various domains. Most probably, the improvement is due to a combination of implementation of population screening, a more restrictive neoadjuvant radiotherapy policy and advances in minimally invasive surgery and organ preserving treatment options.

Long-term restoration of bowel continuity after rectal cancer resection and the influence of surgical technique: A nationwide cross-sectional study.

AIM: Literature on nationwide long-term permanent stoma rates after rectal cancer resection in the minimally invasive era is scarce. The aim of this population-based study was to provide more insight into the permanent stoma rate with interhospital variability (IHV) depending on surgical technique, with pelvic sepsis, unplanned reinterventions and readmissions as secondary outcomes. METHOD: Patients who underwent open or minimally invasive resection of rectal cancer (lower border below the sigmoid take-off) in 67 Dutch centres in 2016 were included in this cross-sectional cohort study. RESULTS: Among 2530 patients, 1470 underwent a restorative resection (58%), 356 a Hartmann's procedure (14%, IHV 0%-42%) and 704 an abdominoperineal resection (28%, IHV 3%-60%). Median follow-up was 51 months. The overall permanent stoma rate at last follow-up was 50% (IHV 13%-79%) and the unintentional permanent stoma rate, permanent stoma after a restorative procedure or an unplanned Hartmann's procedure, was 11% (IHV 0%-29%). A total of 2165 patients (86%) underwent a minimally invasive resection: 1760 conventional (81%), 170 transanal (8%) and 235 robot-assisted (11%). An anastomosis was created in 59%, 80% and 66%, with corresponding unintentional permanent stoma rates of 12%, 24% and 14% (p = 0.001), respectively. When corrected for age, American Society of Anesthesiologists classification, cTNM, distance to the anorectal junction and neoadjuvant (chemo)radiotherapy, the minimally invasive technique was not associated with an unintended permanent stoma (p = 0.071) after a restorative procedure. CONCLUSION: A remarkable IHV in the permanent stoma rate after rectal cancer resection was found. No beneficial influence of transanal or robot-assisted laparoscopy on the unintentional permanent stoma rate was found, although this might be caused by the surgical learning curve. A reduction in IHV and improving preoperative counselling for decision-making for restorative procedures are required.

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.

FixAtion of skiN flaps after mastectomy using ruNning or Interrupted suturEs for combatting seroma: a protocol for a randomised controlled trial (ANNIE).

BACKGROUND: Flap fixation significantly reduces the incidence of seroma formation after mastectomy. Previous studies have compared running sutures, interrupted sutures and tissue glue application with conventional wound closure. A recent systematic review with network meta-analysis showed running sutures to be the most optimal technique; however direct comparisons and high adequate scientific evidence are lacking. This prospective trial aims to directly compare running sutures with interrupted sutures to determine which technique of flap fixation using sutures is superior Methods: This trial will combine a retrospective cohort of patients undergoing flap fixation using interrupted sutures from a previous trial, with a randomised prospective cohort with patients undergoing flap fixation using running sutures or flap fixation using interrupted sutures. This study design was chosen to acquire a sample size with sufficient power and the ability to conduct this study in an acceptable time frame. The primary endpoint is the incidence of complications requiring interventions, including clinically significant seroma, infections and haemorrhagic complications. Secondarily, the length of the procedure and cosmetic results will be compared. DISCUSSION: This is the first trial comparing two suturing techniques for flap fixation after mastectomy. Results will be used to optimise flap fixation techniques for these patients to prevent seroma formation.

Evaluation of National Surgical Practice for Lateral Lymph Nodes in Rectal Cancer in an Untrained Setting.

BACKGROUND: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level. METHODS: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either 'node-picking' (the removal of an individual LLN) or 'partial regional node dissection' (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those  undergoing only rectal resection. RESULTS: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7-3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2-2.5, p = 0.874). CONCLUSION: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.

Watch and wait after neoadjuvant treatment in rectal cancer: comparison of outcomes in patients with and without a complete response at first reassessment in the International Watch & Wait Database (IWWD).

BACKGROUND: In rectal cancer, watch and wait for patients with a cCR after neoadjuvant treatment has an established evidence base. However, there is a lack of consensus on the definition and management of a near-cCR. This study aimed to compare outcomes in patients who achieved a cCR at first reassessment versus later reassessment. METHODS: This registry study included patients from the International Watch & Wait Database. Patients were categorized as having a cCR at first reassessment or at later reassessment (that is near-cCR at first reassessment) based on MRI and endoscopy. Organ preservation, distant metastasis-free survival, and overall survival rates were calculated. Subgroup analyses were done for near-cCR groups based on the response evaluation according to modality. RESULTS: A total of 1010 patients were identified. At first reassessment, 608 patients had a cCR; 402 had a cCR at later reassessment. Median follow-up was 2.6 years for patients with a cCR at first reassessment and 2.9 years for those with a cCR at later reassessment. The 2-year organ preservation rate was 77.8 (95 per cent c.i. 74.2 to 81.5) and 79.3 (75.1 to 83.7) per cent respectively (P = 0.499). Similarly, no differences were found between groups in distant metastasis-free survival or overall survival rate. Subgroup analyses showed a higher organ preservation rate in the group with a near-cCR categorized exclusively by MRI. CONCLUSION: Oncological outcomes for patients with a cCR at later reassessment are no worse than those of patients with a cCR at first reassessment.

Comparison of MRI response evaluation methods in rectal cancer: a multicentre and multireader validation study.

OBJECTIVES: To compare four previously published methods for rectal tumor response evaluation after chemoradiotherapy on MRI. METHODS: Twenty-two radiologists (5 rectal MRI experts, 17 general/abdominal radiologists) retrospectively reviewed the post-chemoradiotherapy MRIs of 90 patients, scanned at 10 centers (with non-standardized protocols). They applied four response methods; two based on T2W-MRI only (MRI tumor regression grade (mrTRG); split-scar sign), and two based on T2W-MRI+DWI (modified-mrTRG; DWI-patterns). Image quality was graded using a 0-6-point score (including slice thickness and in-plane resolution; sequence angulation; DWI b-values, signal-to-noise, and artefacts); scores < 4 were classified below average. Mixed model linear regression was used to calculate average sensitivity/specificity/accuracy to predict a complete response (versus residual tumor) and assess the impact of reader experience and image quality. Group interobserver agreement (IOA) was calculated using Krippendorff's alpha. Readers were asked to indicate their preferred scoring method(s). RESULTS: Average sensitivity/specificity/accuracy was 57%/64%/62% (mrTRG), 36%/79%/66% (split-scar), 40%/79%/67% (modified-mrTRG), and 37%/82%/68% (DWI-patterns); mrTRG showed higher sensitivity but lower specificity and accuracy (p < 0.001) compared to the other methods. IOA was lower for the split scar method (0.18 vs. 0.39-0.43). Higher reader experience had a significant positive effect on diagnostic performance and IOA (except for the split scar sign); below-average imaging quality had a significant negative effect on diagnostic performance. DWI pattern was selected as the preferred method by 73% of readers. CONCLUSIONS: Methods incorporating DWI showed the most favorable results when combining diagnostic performance, IOA, and reader preference. Reader experience and image quality clearly impacted diagnostic performance emphasizing the need for state-of-the-art imaging and dedicated radiologist training. KEY POINTS: • In a multireader study comparing 4 MRI methods for rectal tumor response evaluation, those incorporating DWI showed the best results when combining diagnostic performance, IOA, and reader preference. • The most preferred method (by 73% of readers) was the "DWI patterns" approach with an accuracy of 68%, high specificity of 82%, and group IOA of 0.43. • Reader experience level and MRI quality had an evident effect on diagnostic performance and IOA.

Development and multicenter validation of a multiparametric imaging model to predict treatment response in rectal cancer.

OBJECTIVES: To develop and validate a multiparametric model to predict neoadjuvant treatment response in rectal cancer at baseline using a heterogeneous multicenter MRI dataset. METHODS: Baseline staging MRIs (T2W (T2-weighted)-MRI, diffusion-weighted imaging (DWI) / apparent diffusion coefficient (ADC)) of 509 patients (9 centres) treated with neoadjuvant chemoradiotherapy (CRT) were collected. Response was defined as (1) complete versus incomplete response, or (2) good (Mandard tumor regression grade (TRG) 1-2) versus poor response (TRG3-5). Prediction models were developed using combinations of the following variable groups: (1) Non-imaging: age/sex/tumor-location/tumor-morphology/CRT-surgery interval (2) Basic staging: cT-stage/cN-stage/mesorectal fascia involvement, derived from (2a) original staging reports, or (2b) expert re-evaluation (3) Advanced staging: variables from 2b combined with cTN-substaging/invasion depth/extramural vascular invasion/tumor length (4) Quantitative imaging: tumour volume + first-order histogram features (from T2W-MRI and DWI/ADC) Models were developed with data from 6 centers (n = 412) using logistic regression with the Least Absolute Shrinkage and Selector Operator (LASSO) feature selection, internally validated using repeated (n = 100) random hold-out validation, and externally validated using data from 3 centers (n = 97). RESULTS: After external validation, the best model (including non-imaging and advanced staging variables) achieved an area under the curve of 0.60 (95%CI=0.48-0.72) to predict complete response and 0.65 (95%CI=0.53-0.76) to predict a good response. Quantitative variables did not improve model performance. Basic staging variables consistently achieved lower performance compared to advanced staging variables. CONCLUSIONS: Overall model performance was moderate. Best results were obtained using advanced staging variables, highlighting the importance of good-quality staging according to current guidelines. Quantitative imaging features had no added value (in this heterogeneous dataset). CLINICAL RELEVANCE STATEMENT: Predicting tumour response at baseline could aid in tailoring neoadjuvant therapies for rectal cancer. This study shows that image-based prediction models are promising, though are negatively affected by variations in staging quality and MRI acquisition, urging the need for harmonization. KEY POINTS: This multicenter study combining clinical information and features derived from MRI rendered disappointing performance to predict response to neoadjuvant treatment in rectal cancer. Best results were obtained with the combination of clinical baseline information and state-of-the-art image-based staging variables, highlighting the importance of good quality staging according to current guidelines and staging templates. No added value was found for quantitative imaging features in this multicenter retrospective study. This is likely related to acquisition variations, which is a major problem for feature reproducibility and thus model generalizability.

Delayed TME Surgery in a Watch-and-Wait Strategy After Neoadjuvant Chemoradiotherapy for Rectal Cancer: An Analysis of Hospital Costs and Surgical and Oncological Outcomes.

BACKGROUND: A watch-and-wait strategy for patients with rectal cancer with a clinical complete response after neoadjuvant chemoradiotherapy is a valuable alternative for rectal resection. However, there are patients who will have residual tumor or regrowth during watch and wait. OBJECTIVE: The aim of this study was to investigate safety and costs for patients who underwent delayed surgery after neoadjuvant chemoradiotherapy. DESIGN: This is a retrospective cohort study with prospectively collected data. SETTINGS: The study was conducted at a large teaching hospital. PATIENTS: Between January 2015 and May 2020, 622 new rectal cancer patients were seen, of whom 200 received neoadjuvant chemoradiotherapy. Ninety-four patients were included, 65 of whom underwent immediate surgery and 29 of whom required delayed surgery after an initial watch-and-wait approach. MAIN OUTCOME MEASURES: Outcome measures included 30-day postoperative morbidity rate, hospital costs. 2-year overall and disease-free survival. RESULTS: There was no difference in length of stay (9 vs 8; p = 0.83), readmissions (27.6% vs 10.0%; p = 0.10), surgical re-interventions (15.0% vs 3.4%; p = 0.16), or stoma-free rate (52.6% vs 31.0%; p = 0.09) between immediate and delayed surgery groups. Hospital costs were similar in the delayed group (€11,913 vs €13,769; p = 0.89). Two-year overall survival (93% vs 100%; p = 0.23) and disease-free survival (78% vs 81%; p = 0.47) rates were comparable. LIMITATIONS: Limitations included small sample size, follow-up time and retrospective design. CONCLUSION: Delayed surgery for regrowth in a watch-and-wait program or for persistent residual disease after a repeated assessment is not associated with an increased risk of postoperative morbidity or a significant rise in costs compared to immediate total mesorectal excision. There also appears to be no evident compromise in oncological outcome. Repeated response assessment in patients with a near complete clinical response after neoadjuvant chemoradiotherapy is a useful approach to identify more patients who can benefit from a watch-and-wait strategy. See Video Abstract at http://links.lww.com/DCR/B836 . CIRUGA DE TME RETRASADA EN UNA ESTRATEGIA DE WATCH AND WAIT DESPUS DE LA QUIMIORRADIOTERAPIA NEOADYUVANTE PARA CNCER DE RECTO UN ANLISIS DE COSTOS HOSPITALARIOS, Y DE RESULTADOS QUIRRGICOS Y ONCOLGICOS: ANTECEDENTES: Una estrategia de Watch and Wait para pacientes con cáncer de recto con una respuesta clínica completa después de quimiorradioterapia neoadyuvante es una alternativa valiosa en vez de resección rectal. Sin embargo, hay pacientes que tendrán tumor residual o un recrecimiento durante el Watch and Wait .OBJETIVO: El objetivo fue investigar la seguridad y los costos para los pacientes que se sometieron a una cirugía diferida después de la quimiorradioterapia neoadyuvante.DISEÑO: Este es un estudio de cohorte retrospectivo con datos recolectados prospectivamente.AJUSTE: El estudio se llevó a cabo en un gran hospital universitario.PACIENTES: Entre enero de 2015 y mayo de 2020, se atendieron 622 nuevos pacientes con cáncer de recto, de los cuales 200 recibieron quimiorradioterapia neoadyuvante. Se incluyeron 94 pacientes, de los cuales 65 se sometieron a cirugía inmediata y 29 pacientes requirieron cirugía diferida después de un enfoque inicial de observación y espera.PRINCIPALES MEDIDAS DE RESULTADO: se incluyeron la tasa de morbilidad posoperatoria a 30 días, los costos hospitalarios y las sobrevidas general y libre de enfermedad a dos años.RESULTADOS: No hubo diferencia en la duración de la estancia (9 vs 8, p = 0,83), reingresos (27,6% vs 10,0%, p = 0,10), reintervenciones quirúrgicas (15,0% vs 3,4%, p = 0,16) y tasa libre de estoma (52,6% vs 31,0%, p = 0,09) entre los grupos de cirugía inmediata y tardía. Los costos hospitalarios fueron similares en el grupo retrasado (11913 € frente a 13769 €, p = 0,89). Las tasas de sobrevida general a dos años (93% frente a 100%, p = 0,23) y sobrevida libre de enfermedad (78% frente a 81%, p = 0,47) fueron comparables.LIMITACIONES: Tamaño de muestra pequeño, tiempo de seguimiento y diseño retrospectivo.CONCLUSIÓN: La cirugía tardía para el recrecimiento en un programa de Watch and Wait o para la enfermedad residual persistente después de una evaluación repetida no se asocia con un riesgo mayor de morbilidad posoperatoria ni con un aumento significativo en los costos, en comparación con la escisión total de mesorrecto inmediata. Tampoco parece haber un compromiso evidente en el resultado oncológico. La evaluación repetida de la respuesta en pacientes con una respuesta clínica casi completa después de la quimiorradioterapia neoadyuvante es un enfoque útil para identificar más pacientes que pueden beneficiarse de una estrategia de Watch and Wait . Consulte Video Resumen en http://links.lww.com/DCR/B836 . (Traducción-Dr. Juan Carlos Reyes ).

The Risk of Distant Metastases in Patients With Clinical Complete Response Managed by Watch and Wait After Neoadjuvant Therapy for Rectal Cancer: The Influence of Local Regrowth in the International Watch and Wait Database.

BACKGROUND: Nearly 30% of patients with rectal cancer develop local regrowth after initial clinical complete response managed by watch and wait. These patients might be at higher risk for distant metastases. OBJECTIVE: This study aimed to investigate risk factors for distant metastases using time-dependent analyses. DESIGN: Data from an international watch and wait database were retrospectively reviewed. Cox regression analysis was used to determine risk factors for worse distant metastases-free survival. Conditional survival modeling was used to investigate the impact of risk factors on the development of distant metastases. SETTING: Retrospective, multicenter database. PATIENTS: A total of 793 patients (47 institutions) with rectal cancer and clinical complete response to neoadjuvant treatment from the International Watch & Wait Database were included. MAIN OUTCOME MEASURES: Distant metastases-free survival. RESULTS: Of the 793 patients managed with watch and wait (median follow-up 55.2 mo)' 85 patients (10.7%) had distant metastases. Fifty-one of 85 patients (60%) had local regrowth at any time. Local regrowth was an independent factor associated with worse distant metastases-free survival in the multivariable model. Using conditional estimates, patients with local regrowth without distant metastases for 5 years (from decision to watch and wait) remained at higher risk for development of distant metastases for 1 subsequent year compared to patients without local regrowth (5-year conditional distant metastases-free survival 94.9% vs 98.4%). LIMITATIONS: Lack of information on adjuvant chemotherapy, salvage surgery for local regrowth, and heterogeneity of individual surveillance/follow-up strategies used may have affected results. CONCLUSIONS: In patients with clinical complete response managed by watch and wait, development of local regrowth at any time is a risk factor for distant metastases. The risk of distant metastases remains higher for 5 years after development of local regrowth. See Video Abstract at http://links.lww.com/DCR/C53. EL RIESGO DE METSTASIS A DISTANCIA EN PACIENTES CON RESPUESTA CLNICA COMPLETA MANEJADA POR WATCH AND WAIT DESPUS DE LA TERAPIA NEOADYUVANTE PARA EL CNCER DE RECTO LA INFLUENCIA DEL NUEVO CRECIMIENTO LOCAL EN LA BASE DE DATOS INTERNACIONAL WATCH AND WAIT: ANTECEDENTES:Casi el 30 % de los pacientes con cáncer de recto desarrollan un nuevo crecimiento local después de la respuesta clínica completa inicial manejada por watch and wait. Estos pacientes podrían tener un mayor riesgo de metástasis a distancia.OBJETIVO:Investigar los factores de riesgo de metástasis a distancia mediante análisis dependientes del tiempo.DISEÑO:Se revisó retrospectivamente los datos de la base de datos internacional de Watch and Wait. Se utilizó el análisis de regresión de Cox para determinar los factores de riesgo de peor sobrevida libre de metástasis a distancia. Se utilizó un modelo de sobrevida condicional para investigar el impacto de los factores de riesgo en el desarrollo de metástasis a distancia. El tiempo transcurrido hasta el evento se calculó utilizando la fecha de decisión para watch and wait y la fecha del nuevo crecimiento local para el diagnóstico de metástasis a distancia.ESCENARIOBase de datos multicéntrica retrospectiva.PACIENTES:Se incluyeron un total de 793 pacientes (47 instituciones) con cáncer de recto y respuesta clínica completa al tratamiento neoadyuvante de la base de datos internacional de Watch and Wait.PRINCIPALES MEDIDAS DE RESULTADO:Desarrollo de metástasis a distancia.RESULTADOS:De los 793 pacientes tratados con watch and wait (mediana de seguimiento de 55,2 meses), 85 (10,7%) tenían metástasis a distancia. 51 de 85 (60%) tuvieron recrecimiento local en algún momento. El recrecimiento local fue un factor independiente asociado a una peor supervivencia libre de metástasis a distancia en el modelo multivariable. Además, al usar estimaciones condicionales, los pacientes con recrecimiento local sin metástasis a distancia durante 5 años (desde la decisión de watch and wait) permanecieron en mayor riesgo de desarrollar metástasis a distancia durante un año subsiguiente en comparación con los pacientes sin recrecimiento local (sobrevida libre de metástasis a distancia a 5 años: recrecimiento local 94,9% frente a no recrecimiento local 98,4%).LIMITACIONES:La falta de información relacionada con el uso de quimioterapia adyuvante, las características específicas de la cirugía de rescate para el nuevo crecimient o local y la heterogeneidad de las estrategias individuales de vigilancia/seguimiento utilizadas pueden haber afectado los resultados observados.CONCLUSIONES:En pacientes con respuesta clínica completa manejados por Watch and Wait, el desarrollo de recrecimiento local en cualquier momento es un factor de riesgo para metástasis a distancia. El riesgo de metástasis a distancia sigue siendo mayor durante 5 años después del desarrollo de un nuevo crecimiento local. Consulte Video Resumen en http://links.lww.com/DCR/C53. (Traducción-Dr. Felipe Bellolio).

Technical aspects of flap fixation after mastectomy for breast cancer: Guidelines for improving seroma-related outcome.

OBJECTIVES: Previous studies have identified the added value of flap fixation in reducing seroma formation and its sequelae after mastectomy. The seroma reduction after mastectomy (SAM)-trial proved that sutures were superior to tissue glue. In this article, we will elaborate on the results of the SAM-trial to provide a clear surgical guideline. METHODS: All patients in the suture flap fixation cohort from the SAM-trial were analyzed if details regarding flap fixation were available. The most optimal number of sutures was determined using a receiving operator characteristics curve. The incidence of seroma formation between patients receiving the most optimal number of sutures and patients receiving fewer sutures was compared. RESULTS: The most optimal number of sutures proved to be 15. Patients with ≥15 sutures had a lower incidence of seroma formation at every time frame during follow-up. There was a significant difference at 6 weeks (odds ratio [OR]: 3.05, 95% confidence interval [CI]: 1.09-8.56), 3 months (OR: 4.62, 95% CI: 1.34-12.92), and 1 year postoperatively (OR: 20.48, 95% CI: 2.18-192.22). Ten days and 6 months postoperatively did not differ significantly. CONCLUSIONS: Flap fixation in general, but also the surgical technique influences the incidence of seroma formation after mastectomy. Results suggest a minimum of 15 sutures, spaced approximately 3.7 cm apart.