Oncological Outcomes and Response Rate After Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: A Network Meta-Analysis Comparing Induction vs. Consolidation Chemotherapy vs. Standard Chemoradiation.

TNT is now considered the preferred option for stage II-III locally advanced rectal cancer (LARC). However, the prognostic benefit and optimal sequence of TNT remains unclear. This network meta-analysis (NMA) compared short- and long-term outcomes amongst patients with LARC receiving total neoadjuvant therapy (TNT) as induction (iTNT) or consolidation chemotherapy (cTNT) with those receiving neoadjuvant chemoradiation (nCRT) alone. A systematic literature search was performed between 2012 and 2023. A Bayesian NMA was conducted using a Markov Chain Monte Carlo method with a random-effects model and vague prior distribution to calculate odds ratios (OR) with 95% credible intervals (CrI). The surface under the cumulative ranking (SUCRA) curves were used to rank treatment(s) for each outcome. In total, 11 cohorts involving 8360 patients with LARC were included. There was no significant difference in disease-free survival (DFS) and overall survival (OS) amongst the 3 treatments. Compared with nCRT, both cTNT (OR 2.36; 95% CrI, 1.57-3.66) and iTNT (OR 1.99; 95% CrI, 1.44-2.95) significantly improved complete response (CR) rate. Notably, cTNT ranked as the best treatment for CR (SUCRA 0.90) and iTNT as the best treatment for 3-year DFS and OS (SUCRA 0.72 and 0.87, respectively). Both iTNT and cTNT strategies significantly improved CR rates compared with nCRT. cTNT was ranked highest for CR rates, while iTNT was ranked highest for 3-year survival outcomes. However, no other significant differences in DFS, OS, sphincter-saving surgery, R0 resection and postoperative complications were found amongst the treatment groups.

Pyridostigmine to Reduce the duration of postoperative Ileus after Colorectal surgery (PyRICo-RCT): randomized clinical trial.

BACKGROUND: Postoperative ileus, driven by the cholinergic anti-inflammatory pathway, is the most common complication in patients undergoing colorectal surgery. By inhibiting acetylcholinesterase, pyridostigmine can potentially modulate the cholinergic anti-inflammatory pathway and accelerate gastrointestinal recovery. This study aimed to assess the efficacy of pyridostigmine in improving gastrointestinal recovery after colorectal surgery. METHODS: This double-blinded RCT enrolled adult patients undergoing elective colorectal surgery at two hospitals in South Australia. Patients were randomized to 60 mg oral pyridostigmine or placebo twice daily starting 6 h after surgery until the first passage of stool. The primary outcome was GI-2, a validated composite measure of time to first stool and tolerance of oral diet. Secondary outcomes included incidence of postoperative ileus (defined as GI-2 greater than 4 days), duration of hospital stay, and 30-day complications, evaluated by intention-to-treat univariate analysis. RESULTS: Of 130 patients recruited (mean(s.d.) age 58.4(16.4) years; 73 men, 56%), 65 were allocated to each arm. The median GI-2 was 1 day shorter with pyridostigmine compared with placebo (2 (i.q.r. 1-3) versus 3 (2-4) days; P = 0.015). However, there were no significant differences in postoperative ileus (17.2 versus 21.5%; P = 0.532) or duration of hospital stay (median 5 (i.q.r. 4-8.75) versus 5 (4-7.5) days; P = 0.921). Similarly, there were no significant differences in overall complications, anastomotic leak, cardiac complications, or patient-reported side effects. CONCLUSION: Pyridostigmine resulted in a quicker return of GI-2 and was well tolerated. Larger multicentre studies are required to determine the optimal dosing and evaluate the impact of pyridostigmine in different surgical settings. Registration number: ACTRN12621000530820 (https://anzctr.org.au).

Machine learning prediction model for postoperative ileus following colorectal surgery.

BACKGROUND: Postoperative ileus (POI) continues to be a major cause of morbidity following colorectal surgery. Despite best efforts, the incidence of POI in colorectal surgery remains high (~30%). This study aimed to investigate machine learning techniques to identify risk factors for POI in colorectal surgery patients, to help guide further preventative strategies. METHODS: A TRIPOD-guideline-compliant retrospective study was conducted for major colorectal surgery patients at a single tertial care centre (2018-2022). The primary outcome was the occurrence of POI, defined as not achieving GI-2 (outcome measure of time to first stool and tolerance of oral diet) by day four. Multivariate logistic regression, decision trees, radial basis function and multilayer perceptron (MLP) models were trained using a random allocation of patients to training/testing data sets (80/20). The area under the receiver operating characteristic (AUROC) curves were used to evaluate model performance. RESULTS: Of 504 colorectal surgery patients, 183 (36%) experienced POI. Multivariate logistic regression, decision trees, radial basis function and MLP models returned an AUROC of 0.722, 0.706, 0.712 and 0.800, respectively. The MLP model had the highest sensitivity and specificity values. In addition to well-known risk factors for POI, such as postoperative hypokalaemia, surgical approach, and opioid use, the MLP model identified sarcopenia (ranked 4/30) as a potentially modifiable risk factor for POI. CONCLUSION: MLP outperformed other models in predicting POI. Machine learning can provide valuable insights into the importance and ranking of specific predictive variables for POI. Further research into the predictive value of preoperative sarcopenia for POI is required.

Use of Acetylcholinesterase Inhibitors in Reducing Time to Gastrointestinal Function Recovery following Abdominal Surgery: A Systematic Review.

INTRODUCTION: Postoperative ileus (POI) is a significant complication following abdominal surgery, increasing morbidity and mortality. The cholinergic anti-inflammatory response is one of the major pathways involved in developing POI, but current recommendations to prevent POI do not target this. This review aims to summarise evidence for the use of acetylcholinesterase inhibitors, neostigmine and pyridostigmine, to reduce the time to return of gastrointestinal function (GI) following abdominal surgery. METHODS: A systematic search of various databases was performed from 1946 to May 2023. Randomised controlled trials (RCTs) on acetylcholinesterase inhibitors in intra-abdominal surgery were included. Data on time to flatus and/or stool and side effects were extracted. RESULTS: Among 776 screened manuscripts, 8 RCTs (703 patients) investigating acetylcholinesterase inhibitors in intra-abdominal surgery were analysed. Five studies showed a significant reduction in time to flatus and/or stool by 17-47.6 h. Methodological variations, differing procedure types, and potential bias were observed. Limited studies reported side effects or length of stay. CONCLUSION: Acetylcholinesterase inhibitors may reduce the time for GI to return. However, current evidence is limited and biased. Further studies incorporating acetylcholinesterase inhibitors in an enhanced recovery protocol are required to address this question, especially for patients undergoing colorectal surgery.

Association Between RAS/BRAF Mutations and Complete Response Following Total Neoadjuvant Therapy in Patients with Rectal Cancer: A Prospective Multicentered Study.

BACKGROUND: The impact of RAS/BRAF mutation on primary response rates after total neoadjuvant therapy (TNT) in patients with advanced rectal cancer is unclear. The aim of this study was to assess complete response rates after TNT according to RAS/BRAF mutation status. METHODS: A prospective observational study was performed in patients with rectal cancer who underwent TNT with curative intent at three South Australian hospitals between 2019 and 2023. Patients were classified according to their mutation status: mutant RAS/BRAF (mutRAS) or wild-type RAS/BRAF (wtRAS). The primary endpoint was overall complete response (oCR) rate, defined as the proportion of patients who achieved clinical complete response (cCR) and/or pathological complete response (pCR). RESULTS: Of the 150 patients eligible for inclusion, 80 patients with RAS/BRAF status available were identified. Of these, 43 (53.8%) patients were classified as mutRAS and 37 (46.3%) patients as wtRAS. Patients with mutRAS had significantly lower cCR and oCR rates after TNT than patients with wtRAS (14% vs. 37.8%, p = 0.014; 11.6% vs. 43.2%, p = 0.001, respectively). There was no significant difference in pCR rate between the groups. Of the 80 rectal cancer patients tested, 35 (43.8%) had metastatic disease (M1). There was no significant difference in complete M1 response rates between the groups (17.6% vs. 38.9%, p = 0.254). CONCLUSION: RAS/BRAF mutations negatively impact primary tumor response rates after TNT in patients with advanced rectal cancer. Large-scale national studies are needed to determine whether RAS/BRAF status could be used to select optimal oncologic therapy in rectal cancer patients.

Deep learning to predict lymph node status on pre-operative staging CT in patients with colon cancer.

INTRODUCTION: Lymph node (LN) metastases are an important determinant of survival in patients with colon cancer, but remain difficult to accurately diagnose on preoperative imaging. This study aimed to develop and evaluate a deep learning model to predict LN status on preoperative staging CT. METHODS: In this ambispective diagnostic study, a deep learning model using a ResNet-50 framework was developed to predict LN status based on preoperative staging CT. Patients with a preoperative staging abdominopelvic CT who underwent surgical resection for colon cancer were enrolled. Data were retrospectively collected from February 2007 to October 2019 and randomly separated into training, validation, and testing cohort 1. To prospectively test the deep learning model, data for testing cohort 2 was collected from October 2019 to July 2021. Diagnostic performance measures were assessed by the AUROC. RESULTS: A total of 1,201 patients (median [range] age, 72 [28-98 years]; 653 [54.4%] male) fulfilled the eligibility criteria and were included in the training (n = 401), validation (n = 100), testing cohort 1 (n = 500) and testing cohort 2 (n = 200). The deep learning model achieved an AUROC of 0.619 (95% CI 0.507-0.731) in the validation cohort. In testing cohort 1 and testing cohort 2, the AUROC was 0.542 (95% CI 0.489-0.595) and 0.486 (95% CI 0.403-0.568), respectively. CONCLUSION: A deep learning model based on a ResNet-50 framework does not predict LN status on preoperative staging CT in patients with colon cancer.

Clinical predictors of rectal cancer response after neo-adjuvant (Chemo)Radiotherapy in Australia and New Zealand: Analysis of the Bi-National Colorectal Cancer Audit (BCCA).

Pathological complete response (pCR) is observed in 11-26% of locally advanced rectal cancers undergoing neoadjuvant chemoradiotherapy (nCRT). This study aims to determine pCR rates and clinicopathological predictors in the Australian and New Zealand (ANZ) cohort. The Bi-National Colorectal Cancer Audit (BCCA) was interrogated for all rectal cancer patients who underwent nCRT prior to surgical resection between 2007 and 2020. Patients were divided in two groups: pCR (AJCC tumour regression grade 0) and partial/no response (pPR, regression grade 1,2 or 3). In total, 3230 patients were included. Rates of pCR and pPR were 704 (21.8%) and 2526 (78.2%), respectively. Long-course nCRT (p < 0.0001), lower clinical tumour stage (cT; p < 0.0001), and nodal stage (cN; p = 0.003) were associated with pCR on univariate analysis. On multivariable analysis, cN0 stage and long-course nCRT remained independent factors for a pCR. Awareness of these predictors provides valuable information when counseling patients regarding prognosis and treatment options.

Incidence and associated morbidity of sarcopenia in non-malignant small and large bowel anastomosis: propensity score-matched analysis.

PURPOSE: Sarcopenia is a prognostic factor for poor outcomes in colorectal cancer, but data are scarce in colorectal surgery for benign conditions where patients could benefit from a deferral of surgery to enter a prehabilitation programme. We assessed the incidence of sarcopenia and complications in patients with benign colorectal disease. METHODS: Patients who underwent elective non-malignant colorectal surgery during 2018-2022 were retrospectively identified. The cross-sectional psoas area was calculated using computed tomography (CT) imaging mid-3rd lumbar vertebrae. Sarcopenia was determined using gender-specific cut-offs. The primary outcome was complications measured by the comprehensive complication index (CCI). RESULTS: Of 188 patients identified, 39 (20.7%) were sarcopenic. Patients diagnosed with sarcopenia were older (63 vs. 58 years, p = 0.047) and had a reduced BMI (24.7 vs. 27.38 kg/m2, p = 0.001). Sarcopenic patients had more complications (82.1 vs. 64.4%, p = 0.036), and CCI was statistically but not clinically higher (20.9 vs. 20.9, p = 0.047). On univariate linear regression analysis, age ≥ 65 years old, ASA grade ≥ 3, active smokers, sarcopenia, and preoperative anaemia were predictive of CCI. Propensity score-matched analysis was performed, matching 78 cases to remove selection bias, which demonstrated sarcopenia had no impact on postoperative complications. On multivariate analysis, age (p = 0.022), smoking (p = 0.005), and preoperative anaemia (p = 0.008) remained predictive of CCI. CONCLUSION: Sarcopenia is prevalent in one-fifth of patients undergoing benign colorectal surgery. Taking advantage of the longer preoperative waiting periods, sarcopenia could be explored as a target for prehabilitation programmes to improve outcomes.

Global cost of postoperative ileus following abdominal surgery: meta-analysis.

BACKGROUND: Following abdominal surgery, postoperative ileus is a common complication significantly increasing patient morbidity and cost of hospital admission. This is the first systematic review aimed at determining the average global hospital cost per patient associated with postoperative ileus. METHODS: A systematic search of electronic databases was performed from January 2000 to March 2023. Studies included compared patients undergoing abdominal surgery who developed postoperative ileus to those who did not, focusing on costing data. The primary outcome was the total cost of inpatient stay. Risk of bias was assessed using the Newcastle-Ottawa assessment tool. Summary meta-analysis was performed. RESULTS: Of the 2071 studies identified, 88 papers were assessed for full eligibility. The systematic review included nine studies (2005-2022), investigating 1 860 889 patients undergoing general, colorectal, gynaecological and urological surgery. These studies showed significant variations in the definition of postoperative ileus. Six studies were eligible for meta-analysis showing an increase of €8233 (95 per cent c.i. (5176 to 11 290), P < 0.0001, I2 = 95.5 per cent) per patient with postoperative ileus resulting in a 66.3 per cent increase in total hospital costs (95 per cent c.i. (34.8 to 97.9), P < 0.0001, I2 = 98.4 per cent). However, there was significant bias between studies. Five colorectal-surgery-specific studies showed an increase of €7242 (95 per cent c.i. (4502 to 9983), P < 0.0001, I2 = 86.0 per cent) per patient with postoperative ileus resulting in a 57.3 per cent increase in total hospital costs (95 per cent c.i. (36.3 to 78.3), P < 0.0001, I2 = 85.7 per cent). CONCLUSION: The global financial burden of postoperative ileus following abdominal surgery is significant. While further multicentre data using a uniform postoperative ileus definition would be useful, reducing the incidence and impact of postoperative ileus are a priority to mitigate healthcare-related costs, and improve patient outcomes.

Is preoperative sarcopenia associated with postoperative complications after pelvic exenteration surgery?

PURPOSE: Pelvic exenteration (PE) involves radical surgical resection of pelvic organs and is associated with considerable morbidity. Sarcopenia is recognised as a predictor of poor surgical outcomes. This study aimed to determine if preoperative sarcopenia is associated with postoperative complications after PE surgery. METHODS: This retrospective study included patients who underwent PE with an available preoperative CT scan between May 2008 and November 2022 at the Royal Adelaide Hospital and St. Andrews Hospital in South Australia. Total Psoas Area Index (TPAI) was estimated by measuring the cross-sectional area of the psoas muscles at the level of the third lumbar vertebra on abdominal CT, normalised for patient height. Sarcopenia was diagnosed based on gender-specific TPAI cut-off values. Logistic regression analyses were performed to identify risk factors for major postoperative complications with a Clavien-Dindo (CD) grade ≥ 3. RESULTS: In total, 128 patients who underwent PE were included, 90 of whom formed the non-sarcopenic group (NSG) and 38 the sarcopenic group (SG). Major postoperative complications (CD grade ≥ 3) occurred in 26 (20.3%) patients. There was no detectable association with sarcopenia and an increased risk of major postoperative complications. Preoperative hypoalbuminemia (P = 0.01) and a prolonged operative time (P = 0.002) were significantly associated with a major postoperative complication on multivariate analysis. CONCLUSION: Sarcopenia is not a predictor of major postoperative complications in patients undergoing PE surgery. Further efforts aimed specifically at optimising preoperative nutrition may be warranted.

Can sarcopenia predict complete response after total neoadjuvant therapy in advanced rectal cancer? A multicentre observational cohort study.

BACKGROUND: The association between sarcopenia and response to neoadjuvant treatment remains unclear. This study investigates sarcopenia as a predictor of overall complete response (oCR) after Total Neoadjuvant Therapy (TNT) for advanced rectal cancer. METHOD: A prospective observational study was performed of patients with rectal cancer undergoing TNT at three South Australian hospitals between 2019 and 2022. Sarcopenia was diagnosed by pretreatment computed tomography measurement of psoas muscle cross-sectional area at the third lumbar vertebra level, normalised for patient height. The primary endpoint was oCR rate defined as the proportion of patients who achieved either clinical complete response (cCR) or pathological complete response. RESULTS: This study included 118 rectal cancer patients with an average age of 59.5 years, 83 (70.3%) of whom formed the non-sarcopenic group (NSG) and 35 (29.7%) the sarcopenic group (SG). The oCR rate was significantly higher in NSG compared with the SG (p < 0.001). cCR rate was significantly greater in NSG compared with the SG (p = 0.001). Multivariate analysis revealed sarcopenia (p = 0.029) and hypoalbuminemia (p = 0.040) were risk factors for cCR and sarcopenia was an independent risk factor for oCR (p = 0.020). CONCLUSION: Sarcopenia and hypoalbuminemia were negatively associated with tumour response following TNT in advanced rectal cancer patients.

A prospective study of diagnostic accuracy of multidisciplinary team and radiology reporting of preoperative colorectal cancer local staging.

INTRODUCTION: The aim of this study was to correlate and assess diagnostic accuracy of preoperative staging at multidisciplinary team meeting (MDT) against the original radiology reports and pathological staging in colorectal cancer patients. METHODS: A prospective observational study was conducted at two institutions. Patients with histologically proven colorectal cancer and available preoperative imaging were included. Preoperative tumor and nodal staging (cT and cN) as determined by the MDT and the radiology report (computed tomography [CT] and/or magnetic resonance imaging [MRI]) were recorded. Kappa statistics were used to assess agreement between MDT and the radiology report for cN staging in colon cancer, cT and cN in rectal cancer, and tumor regression grade (TRG) in patients with rectal cancer who received neoadjuvant therapy. Pathological report after surgery served as the reference standard for local staging, and AUROC curves were constructed to compare diagnostic accuracy of the MDT and radiology report. RESULTS: A total of 481 patients were included. Agreement between MDT and radiology report for cN stage was good in colon cancer (k = .756, Confidence Interval (CI) 95% .686-.826). Agreement for cT and cN and in rectal cancer was very good (kw = .825, CI 95% .758-.892) and good (kw = .792, CI 95% .709-.875), respectively. In the rectal cancer group that received neoadjuvant therapy, agreement on TRG was very good (kw = .919, CI 95% .846-.993). AUROC curves using pathological staging indicated no difference in diagnostic accuracy between MDT and radiology reports for either colon or rectal cancer. CONCLUSION: Preoperative colorectal cancer local staging was consistent between specialist MDT review and original radiology reports, with no significant differences in diagnostic accuracy identified.

Outcomes of open vs laparoscopic vs robotic vs transanal total mesorectal excision (TME) for rectal cancer: a network meta-analysis.

BACKGROUND: Total mesorectal excision (TME) for rectal cancer can be achieved using open (OpTME), laparoscopic (LapTME), robotic (RoTME), or transanal techniques (TaTME). However, the optimal approach for access remains controversial. The aim of this network meta-analysis was to assess operative and oncological outcomes of all four surgical techniques. METHODS: Ovid MEDLINE, EMBASE, and PubMed databases were searched systematically from inception to September 2020, for randomised controlled trials (RCTs) comparing any two TME surgical techniques. A network meta-analysis using a Bayesian random-effects framework and mixed treatment comparison was performed. Primary outcomes were the rate of clear circumferential resection margin (CRM), defined as > 1 mm from the closest tumour to the cut edge of the tissue, and completeness of mesorectal excision. Secondary outcomes included radial and distal resection margin distance, postoperative complications, locoregional recurrence, disease-free survival, and overall survival. Surface under cumulative ranking (SUCRA) was used to rank the relative effectiveness of each intervention for each outcome. The higher the SUCRA value, the higher the likelihood that the intervention is in the top rank or one of the top ranks. RESULTS: Thirty-two RCTs with a total of 6151 patients were included. Compared with OpTME, there was no difference in the rates of clear CRM: LapTME RR = 0.99 (95% (Credible interval) CrI 0.97-1.0); RoTME RR = 1.0 (95% CrI 0.96-1.1); TaTME RR = 1.0 (95% CrI 0.96-1.1). There was no difference in the rates of complete mesorectal excision: LapTME RR = 0.98 (95% CrI 0.98-1.1); RoTME RR = 1.1 (95% CrI 0.98-1.4); TaTME RR = 1.0 (95% CrI 0.91-1.2). RoTME was associated with improved distal resection margin distance compared to other techniques (SUCRA 99%). LapTME had a higher rate of conversion to open surgery when compared with RoTME: RoTME RR = 0.23 (95% CrI 0.034-0.70). Length of stay was shortest in RoTME compared to other surgical approaches: OpTME mean difference in days (MD) 3.3 (95% CrI 0.12-6.0); LapTME MD 1.7 (95% CrI - 1.1-4.4); TaTME MD 1.3 (95% CrI - 5.2-7.4). There were no differences in 5-year overall survival (LapTME HR 1.1, 95% CrI 0.74, 1.4; TaTME HR 1.7, 95% CrI 0.79, 3.4), disease-free survival rates (LapTME HR 1.1, 95% CrI 0.76, 1.4; TaTME HR 1.1, 95% CrI 0.52, 2.4), or anastomotic leakage (LapTME RR = 0.92 (95% CrI 0.63, 1.1); RoTME RR = 1.0 (95% CrI 0.48, 1.8); TaTME RR = 0.53 (95% CrI 0.19, 1.2). The overall quality of evidence as per Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessments across all outcomes including primary and secondary outcomes was deemed low. CONCLUSIONS: In selected patients eligible for a RCT, RoTME achieved improved distal resection margin distance and a shorter length of hospital stay. No other differences were observed in oncological or recovery parameters between (OpTME), laparoscopic (LapTME), robotic (RoTME), or trans-anal TME (TaTME). However, the overall quality of evidence across all outcomes was deemed low.

Does Sarcopenia Predict Local Response Rates After Chemoradiotherapy for Locally Advanced Rectal Cancer?

BACKGROUND: The predictive value of sarcopenia for tumor response to neoadjuvant chemoradiotherapy is unclear. OBJECTIVE: This study aimed to investigate the association between sarcopenia and pathological tumor regression grade after neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. DESIGN: Retrospective cohort study from a prospectively collected database. Univariate logistic regression was performed to assess the association between sarcopenia and tumor response. SETTINGS: This study was conducted at 2 tertiary care centers. PATIENTS: Participants were patients undergoing neoadjuvant chemoradiotherapy for locally advanced rectal cancer (T3/4, N0/+) between 2007 and 2018. INTERVENTION: Sarcopenia was diagnosed using sex-specific cutoffs of lean muscle mass. Using the initial staging CT, lean muscle mass was estimated using the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra, normalized for patient height. MAIN OUTCOME MEASURES: The primary end point was pathological tumor regression grade, defined as good (tumor regression grade 0/1) vs poor (tumor regression grade 2/3). RESULTS: The study included 167 patients with locally advanced rectal cancer with a median age of 60 (20-91) years, with 132 in the nonsarcopenia group and 35 in the sarcopenia group. Eighty-nine percent of patients had stage 3 cancer. Nine patients (5.4%) had a complete clinical response, 1 patient did not respond to treatment and opted for nonoperative management, and the remaining 157 patients (94.0%) proceeded to surgery. Pathological data revealed no significant difference between good tumor regression grade patients in the sarcopenia group compared with the nonsarcopenia group. Univariate analysis revealed BMI ≥25 kg/m 2 to be a risk factor for good tumor regression grade ( p = 0.002). LIMITATIONS: This study was limited by its retrospective design and small sample size. CONCLUSIONS: Sarcopenia is not a predictor of poor neoadjuvant chemoradiotherapy response in patients with locally advanced rectal cancer. Increasing BMI was associated with good tumor regression grade. Future multicentered studies are warranted to validate this finding. See Video Abstract at http://links.lww.com/DCR/C78 . LA SARCOPENIA PREDICE LAS TASAS DE RESPUESTA LOCAL DESPUS DE LA QUIMIORRADIOTERAPIA PARA EL CNCER DE RECTO LOCALMENTE AVANZADO: ANTECEDENTES:El valor predictivo de la sarcopenia para la respuesta tumoral a la quimiorradioterapia neoadyuvante no está claro.OBJETIVO:Este estudio investiga la asociación entre la sarcopenia y el grado de regresión tumoral patológica después de la quimiorradioterapia neoadyuvante en pacientes con cáncer de recto localmente avanzado.DISEÑO:Estudio de cohorte retrospectivo a partir de una base de datos recolectada prospectivamente. Se realizó una regresión logística univariante para evaluar la asociación entre la sarcopenia y la respuesta tumoral.ENTORNO CLINICO:Este estudio se realizó en dos centros de atención terciaria.PACIENTES:Pacientes sometidos a quimiorradioterapia neoadyuvante por cáncer de recto localmente avanzado (T3/4, N0/+) entre 2007-2018.INTERVENCIÓNES:La sarcopenia se diagnosticó utilizando puntos de corte de masa muscular magra específicos por género. Utilizando la tomografía computarizada de estadificación inicial, se estimó la masa muscular magra utilizando el área transversal del músculo psoas a nivel de la tercera vértebra lumbar, normalizada para la altura del paciente.PRINCIPALES MEDIDAS DE VALORACIÓN:El criterio principal de valoración fue el grado de regresión tumoral patológica, definido como bueno (grado de regresión tumoral 0/1) frente a malo (grado de regresión tumoral 2/3).RESULTADOS:El estudio incluyó a 167 pacientes con cáncer de recto localmente avanzado con una mediana de edad de 60 años (20-91), 132 en el grupo sin sarcopenia y 35 en el grupo con sarcopenia. Ochenta y nueve por ciento estaban en etapa III. Seis pacientes (5,4%) tuvieron respuesta clínica completa sostenida, un paciente no respondió al tratamiento y optó por manejo conservador, los 157 restantes (94,0%) procedieron a cirugía. Los datos patológicos no revelaron diferencias significativas entre los pacientes con buen grado de regresión tumoral en el grupo de sarcopenia en comparación con el grupo sin sarcopenia. El análisis univariado reveló que un IMC ≥25 kg/m2 era un factor de riesgo para un buen grado de regresión tumoral (p = 0,002).LIMITACIONES:Este estudio estuvo limitado por su diseño retrospectivo y tamaño de muestra pequeño.CONCLUSIÓNES:La sarcopenia no es un predictor de mala respuesta a la quimiorradioterapia neoadyuvante en pacientes con cáncer de recto localmente avanzado. El aumento del IMC se asoció con un buen grado de regresión tumoral. Se justifican futuros estudios multicéntricos para validar este hallazgo. Consulte Video Resumen en http://links.lww.com/DCR/C78 . (Traducción-Dr. Ingrid Melo ).

Personalized total neoadjuvant therapy versus chemotherapy during the 'wait period' versus standard chemoradiotherapy for locally advanced rectal cancer.

BACKGROUND: This study aimed to compare current treatment response rates with personalized Total Neoadjuvant Therapy (pTNT), against extended chemotherapy in the 'wait period' (xCRT) and standard chemoradiotherapy (sCRT) with adjuvant chemotherapy for rectal cancer. METHODS: This was a multicentre retrospective cohort analysis. Consecutive patients with rectal cancer treated with pTNT over a 3.9-year period were compared to a historical cohort of patients treated with xCRT or sCRT as part of the published WAIT Trial. pTNT patients received 8 cycles mFOLFOX6 or 6 cycles CAPOX in the neoadjuvant setting (no adjuvant treatment). Patients in the WAIT Trial received either 3 cycles 5-FU/LV during the 10-week wait period after chemoradiotherapy or standard chemoradiotherapy, followed by adjuvant chemotherapy. The primary endpoint was overall complete response (oCR) rate defined as the proportion of patients who achieved either complete clinical response (cCR) or pathological complete response (pCR). RESULTS: Of 284 patients diagnosed with rectal cancer during the 3.9-year period, 107 received pTNT. Forty of these were matched with 49 patients from the WAIT Trial (25 received xCRT and 24 received sCRT). There was a significant difference in oCR between the groups (pTNT n = 21, xCRT n = 6, sCRT n = 7, P = 0.043). Of the patients that underwent surgery, pCR occurred in 13 patients with no significant difference between groups (P = 0.415). There were no significant differences in 2-year disease-free survival or overall survival. CONCLUSION: Compared with sCRT and xCRT, pTNT results in a significantly higher complete response rate which may facilitate organ preservation.

Clinical and biochemical predictors of tumor response after neoadjuvant therapy in rectal cancer.

BACKGROUND: Patients who have a good clinical and/or pathologic response to neoadjuvant chemoradiotherapy (nCRT) for rectal cancer have better long-term outcomes and can potentially be spared morbid surgery. This study aimed to identify pretreatment clinical and biochemical predictors of response to neoadjuvant treatment for rectal cancer. METHODS: Patients undergoing neoadjuvant therapy for rectal cancer between 2007 and 2022 were retrospectively included. Those patients who achieved a complete clinical response were offered a nonoperative management strategy and the remaining patients underwent surgical resection. The primary endpoint was tumor regression grade (TRG) based on radiological imaging (mrTRG) or pathology (pTRG). Patient response was classified as good (mrTRG 1-2 or pTRG 0-1) versus poor (mrTRG 3-4 or pTRG 2-3). Logistic regression was performed to determine predictors of TRG. RESULTS: A total of 984 patients with rectal cancer were identified of which 274 met the inclusion criteria. Of 274 patients, 228 (83%) underwent surgical resection. A good TRG response was observed in 119 (41%) patients, and a complete response was achieved in 53 (17%) patients. On univariable and multivariable logistic regression, clinical T2 stage and body mass index of ≥25 kg/m2 were significant predictors of a good TRG. Clinical T2 stage and a personalised total neoadjuvant therapy regimen were significant predictors of complete response. CONCLUSION: Clinical T2 stage and a BMI≥25 kg/m2 were predictors of good response to neoadjuvant therapy for rectal cancer. Future prospective studies are required to confirm these findings and evaluate their potential use in better targeting of nCRT.

Personalized total neoadjuvant therapy (pTNT) for advanced rectal cancer with tailored treatment sequencing based on clinical stage at presentation.

BACKGROUND: This study aimed to assess short-term outcomes of a personalized total neoadjuvant treatment (pTNT) protocol, with treatment sequencing based on clinical stage at presentation. METHODS: A multidisciplinary pTNT protocol was implemented across two metropolitan hospitals. This consists of two-schema based on clinical stage: patients with distant failure risk were offered induction chemotherapy before chemoradiation (nCRT), and patients with locoregional failure risk received nCRT followed by consolidation chemotherapy. Patients underwent surgical resection unless a complete clinical response (cCR) was achieved, in which case non-operative management (NOM) was offered. A prospective cohort analysis of all patients with rectal cancer who underwent pTNT with curative intent between Jan 2019 and Aug 2022 was performed. RESULTS: Of 270 patients referred with rectal cancer, 102 received pTNT with curative intent and 79 have completed their treatment thus far. Thirty-three patients (41.8%) received induction chemotherapy and 46 (58.2%) received consolidation chemotherapy per protocol. The percentage of patients with EMVI, resectable M1 disease, cT4 disease, and positive lateral lymph nodes were 54.4%, 36.7%, 27.8% and 15.2%, respectively. Overall, 32 (40.5%) patients had cCR and 4 (5.1%) pCR, and 40 (50.6%) patients had non-operative management. Grade 3 toxicity was reported in 10.1% of patients and only three patients (3.8%) experienced Grade 4 chemotherapy-related toxicity, with no treatment related mortality. CONCLUSION: Early results with a defined two-schema pTNT protocol are encouraging and suggest that tailoring sequencing to disease risk at presentation may represent the optimal balance between local and distant disease control, as well as treatment toxicity.

Short-term outcomes following development of a dedicated pelvic exenteration service in a tertiary centre.

BACKGROUND: Pelvic exenteration surgery (PE) offers potentially curative resection for locally advanced malignancy but is associated with significant complexity and morbidity. Specialised teams are recommended to achieve optimal patient outcomes. This study aims to analyse short-term outcomes at a tertiary setting before and after creating a dedicated PE service. METHODS: Patients undergoing PE between 2008 and October 2021 at the Royal Adelaide Hospital and St. Andrews Hospital in South Australia were included, with prospective data collection since June 2017. Patients operated on prior and post the creation of the PE service were compared via univariate analyses. RESULTS: In total, 113 patients were included, with a significant increase in volume of cases post creation of the PE service, (n = 46 pre versus n = 67 post). There were significant differences in the type of neoadjuvant therapy and patient co-morbidity, with more advanced disease stage and a higher likelihood of bone involvement (P < 0.05) in the latter period. An increased proportion of patients had flap reconstruction (40.3 versus 33.9%, P = 0.010) as well as lateral lymph node dissection (13.4 versus 2.2%, P = 0.046). Despite this, peri-operative outcomes such as urosepsis (11.9 versus 28.3%, P = 0.028) and Clavien-Dindo grade of complications grade improved. R0 resections were achieved in 93.9% of curative cases (93.9 versus 84.2%, P = 0.171). CONCLUSION: The development of a PE service significantly improved short term patient outcomes, despite the inclusion of patients with more advanced disease and comorbidity.