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OBJECTIVE: To assess the effect of a practice-level preoperative frailty screening and optimization toolkit (OPTI-Surg) on postoperative functional recovery and complications in elderly cancer patients undergoing major surgery. SUMMARY BACKGROUND DATA: Frailty is common in older adults. it increases risk for poor postoperative functional recovery and complications. The potential for a practice-level screening/optimization intervention to improve outcomes is unknown. METHODS: Thoracic, gastrointestinal, and urologic oncological surgery practices within the NCI Community Oncology Research Program (NCORP) were randomized 1:1:1, to usual care (UC), OPTI-Surg, or OPTI-Surg with implementation coach. OPTI-Surg consisted of the Edmonton Frail Scale and guided recommendations for referral interventions. Patients ≥70 years old undergoing curative intent surgery were eligible. Primary outcome was 8 weeks postoperative function (kCal/week). Key secondary outcome was complications within 90 days. Mixed models were used to compare UC to the 2 OPTI-Surg arms combined. RESULTS: From 7/2019 to 9/2022, 325 patients were enrolled from 29 practices. 199 (64 UC, 135 OPTI-Surg) and 279 (78 UC, 201 OPTI-Surg) were evaluable for primary and secondary analysis, respectively. UC and OPTI-Surg patients did not significantly differ on total caloric expenditure (2.2 UC, 2.0 OPTI-Surg) after adjusting for baseline function (P=0.53). UC and OPTI-Surg patients did not significantly differ on postoperative complications (25.6% UC, 35.3% OPTI-Surg, P=0.5). CONCLUSIONS: Frailty assessment was successfully performed, but the OPTI-Surg intervention did not improve postoperative function nor reduce postoperative complications compared to UC. Future analysis will explore practice-level factors associated with toolkit implementation and differences between the coaching and non-coaching arms.
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This cross-sectional study assesses the impact of changes to medical billing and coding work relative value units in 2021.
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BACKGROUND: Lateral pelvic lymph-node dissection is performed for selected patients with rectal cancer with persistent lateral nodal disease after neoadjuvant therapy. This technique has been slow to be adopted in the West due to concerns regarding technical difficulty. This is the first report on the learning curve for lateral pelvic lymph node dissection in the US or Europe. OBJECTIVE: The aim of this study was to analyze the learning curve associated with robotic lateral pelvic lymph node dissection. DESIGN: Retrospective observational cohort. SETTING: Tertiary academic cancer center. PATIENTS: Consecutive patients from 2012 to 2021. INTERVENTION: All patients underwent robotic lateral pelvic lymph node dissection. MAIN OUTCOME MEASURES: The primary endpoints were the learning curves for maximum number of nodes retrieved and urinary retention which was evaluated with simple cumulative-sum and two-sided Bernoulli cumulative-sum charts. RESULTS: Fifty-four procedures were included. A single-surgeon (n = 35) and an institutional learning curve are presented in the analysis. In the single-surgeon learning curve, a turning point marking the end of a learning phase was detected at the 12th procedure for the number of retrieved nodes and at the 20th for urinary retention. In the institutional learning curve analysis, two turning points were identified at the 13th and 26th procedures indicating progressive improvements for the number of retrieved nodes and at the 27th for urinary retention. No sustained alarm signals were detected at any time point. LIMITATIONS: The retrospective nature, small sample size and the referral center nature of the reporting institution that may limit generalizability. CONCLUSIONS: In a setting of institutional experience with robotic colorectal surgery including beyond TME resections, the learning curve for robotic lateral pelvic lymph node dissection is acceptably short. Our results demonstrate feasibility of acquisition of this technique in a controlled setting, with sufficient case volume and proctoring can optimize the learning curve. See Video Abstract.
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BACKGROUND: Early predictors of postoperative complications can risk-stratify patients undergoing colorectal cancer surgery. However, conventional regression models have limited power to identify complex nonlinear relationships among a large set of variables. We developed artificial neural network models to optimize the prediction of major postoperative complications and risk of readmission in patients undergoing colorectal cancer surgery. OBJECTIVE: The aim of this study was to develop an artificial neural network model to predict postoperative complications using postoperative laboratory values, and compare these models' accuracy to standard regression methods. DESIGN: This retrospective study included patients who underwent elective colorectal cancer resection between January 1, 2016, and July 31, 2021. Clinical data, cancer stage, and laboratory data from postoperative day 1 to 3 were collected. Models of complications and readmission risk were created using multivariable logistic regression and single-layer neural networks. SETTING: National Cancer Institute-Designated Comprehensive Cancer Center. PATIENTS: Adult colorectal cancer patients. MAIN OUTCOME MEASURES: Accuracy of predicting postoperative major complication, readmission and anastomotic leak using the area under the receiver-operating characteristic curve. RESULTS: Neural networks had larger areas under the curve for predicting major complications compared to regression models (neural network 0.811; regression model 0.724, p < 0.001). Neural networks also showed an advantage in predicting anastomotic leak (p = 0.036) and readmission using postoperative day 1-2 values (p = 0.014). LIMITATIONS: Single-center, retrospective design limited to cancer operations. CONCLUSIONS: In this study, we generated a set of models for early prediction of complications after colorectal surgery. The neural network models provided greater discrimination than the models based on traditional logistic regression. These models may allow for early detection of postoperative complications as soon as postoperative day 2. See Video Abstract.
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Total neoadjuvant therapy (TNT) is a novel strategy for rectal cancer that administers both (chemo)radiotherapy and systemic chemotherapy before surgery. TNT is expected to improve treatment compliance, tumor regression, organ preservation, and oncologic outcomes. Multiple TNT regimens are currently available with various combinations of the treatments including induction or consolidation chemotherapy, triplet or doublet chemotherapy, and long-course chemoradiotherapy or short-course radiotherapy. Evidence on TNT is rapidly evolving with new data on clinical trials, and no definitive consensus has been established on which regimens to use for improving outcomes. Clinicians need to understand the advantages and limitations of the available regimens for multidisciplinary decision making. This article reviews currently available evidence on TNT for rectal cancer. A decision making flow chart is provided for tailor-made use of TNT regimens based on tumor location and local and systemic risk.
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INTRODUCTION: In colorectal cancer, the presence of para-aortic lymph nodes (PALN) indicates extraregional disease. Appropriately selecting patients for whom PALN dissection will provide oncologic benefit remains challenging. This study identified factors to predict survival among patients undergoing PALN dissection for colorectal cancer. METHODS: An institutional database was queried for patients who underwent curative-intent resection of clinically positive PALN for colorectal cancer between 2007 and 2020. Preoperative radiologic images were reviewed, and patients who did and did not have positive PALN on final pathology were compared. Survival analysis was performed to evaluate the impact of pathologically positive PALN on recurrence-free (RFS) and overall survival (OS). RESULTS: Of 74 patients who underwent PALN dissection, 51 had PALN metastasis at the time of primary tumor diagnosis, whereas 23 had metachronous PALN disease. Preoperative chemotherapy ± radiotherapy was given in 60 cases (81.1%), and 28 (37.8%) had pathologically positive PALN. Independent factors associated with positive PALN pathology included metachronous PALN disease and pretreatment and posttreatment radiographically abnormal PALN. On multivariable analysis, pathologically positive PALN was significantly associated with decreased RFS (hazard ratio 3.90) and OS (HR 4.49). Among patients with pathologically positive PALN, well/moderately differentiated histology was associated with better OS, and metachronous disease trended toward an association with better OS. CONCLUSIONS: Pathologically positive PALN are associated with poorer RFS and OS after PALN dissection for colorectal cancer. Clinicopathologic factors may predict pathologic PALN positivity. Curative-intent surgery may provide benefit, especially in patients with well-to-moderately differentiated primary tumors and possibly metachronous PALN disease.
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Neoplasias Colorretais , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Humanos , Masculino , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/mortalidade , Feminino , Idoso , Pessoa de Meia-Idade , Taxa de Sobrevida , Linfonodos/patologia , Linfonodos/cirurgia , Estudos Retrospectivos , Seguimentos , Prognóstico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgiaRESUMO
Background: Postoperative ileus (POI) is a common complication after colorectal surgery, leading to increased hospital stay and costs. This study aimed to explore patient comorbidities that contribute to the development of POI in the colorectal surgical population and compare machine learning (ML) model accuracy to existing risk instruments. Study Design: In a retrospective study, data were collected on 316 adult patients who underwent colorectal surgery from January 2020 to December 2021. The study excluded patients undergoing multi-visceral resections, re-operations, or combined primary and metastatic resections. Patients lacking follow-up within 90 days after surgery were also excluded. Eight different ML models were trained and cross-validated using 29 patient comorbidities and four comorbidity risk indices (ASA Status, NSQIP, CCI, and ECI). Results: The study found that 6.33% of patients experienced POI. Age, BMI, gender, kidney disease, anemia, arrhythmia, rheumatoid arthritis, and NSQIP score were identified as significant predictors of POI. The ML models with the greatest accuracy were AdaBoost tuned with grid search (94.2%) and XG Boost tuned with grid search (85.2%). Conclusions: This study suggests that ML models can predict the risk of POI with high accuracy and may offer a new frontier in early detection and intervention for postoperative outcome optimization. ML models can greatly improve the prediction and prevention of POI in colorectal surgery patients, which can lead to improved patient outcomes and reduced healthcare costs. Further research is required to validate and assess the replicability of these results.
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Íleus , Aprendizado de Máquina , Complicações Pós-Operatórias , Humanos , Feminino , Íleus/etiologia , Complicações Pós-Operatórias/etiologia , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Cirurgia Colorretal/efeitos adversos , Fatores de Risco , AdultoRESUMO
PURPOSE: Dynamic operations platforms allow for cross-platform data extraction, integration, and analysis, although application of these platforms to large-scale oncology enterprises has not been described. This study presents a pipeline for automated, high-fidelity extraction, integration, and validation of cross-platform oncology data in patients undergoing treatment for rectal cancer at a single, high-volume institution. METHODS: A dynamic operations platform was used to identify patients with rectal cancer treated at MD Anderson Cancer Center between 2016 and 2022 who had magnetic resonance imaging (MRI) imaging and preoperative treatment details available in the electronic health record (EHR). Demographic, clinicopathologic, tumor mutation, radiographic, and treatment data were extracted from the EHR using a methodology adaptable to any disease site. Data accuracy was assessed by manual review. Accuracy before and after implementation of synoptic reporting was determined for MRI data. RESULTS: A total of 516 patients with localized rectal cancer were included. In the era after institutional adoption of synoptic reports, the dynamic operations platform extracted T (tumor) category data from the EHR with 95% accuracy compared with 87% before the use of synoptic reports, and N (lymph node) category with 88% compared with 58%. Correct extraction of pelvic sidewall adenopathy was 94% compared with 78%, and extramural vascular invasion accuracy was 99% compared with 89%. Neoadjuvant chemotherapy and radiation data were 99% accurate for patients who had synoptic data sources. CONCLUSION: Using dynamic operations platforms enables automated cross-platform integration of multiparameter oncology data with high fidelity in patients undergoing multimodality treatment for rectal cancer. These pipelines can be adapted to other solid tumors and, together with standardized reporting, can increase efficiency in clinical research and the translation of actionable findings toward optimizing patient outcomes.
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Bases de Dados Factuais , Imageamento por Ressonância Magnética , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Idoso , Registros Eletrônicos de Saúde , Adulto , Reprodutibilidade dos Testes , Estadiamento de NeoplasiasRESUMO
With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.
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Multidisciplinary management of rectal cancer has rapidly evolved over the last several years. This review describes recent data surrounding total neoadjuvant therapy, organ preservation, and management of lateral pelvic lymph nodes. It then presents our treatment algorithm for management of rectal cancer at The University of Texas MD Anderson Cancer Center in the context of this and other existing literature. As part of this discussion, the review describes how we tailor management based upon both patient and tumor-related factors in an effort to optimize patient outcomes.
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AIM: As multidisciplinary treatment strategies for colorectal cancer have improved, aggressive surgical resection has become commonplace. Multivisceral and extended resections offer curative-intent resection with significant survival benefit. However, limited data exist regarding the feasibility and oncological efficacy of performing extended resection via a minimally invasive approach. The aim of this study was to determine the perioperative and long-term outcomes following robotic extended resection for colorectal cancer. METHOD: We describe the population of patients undergoing robotic multivisceral resection for colorectal cancer at our single institution. We evaluated perioperative details and investigated short- and long-term outcomes, using the Kaplan-Meier method to analyse overall and recurrence-free survival. RESULTS: Among the 86 patients most tumours were T3 (47%) or T4 (47%) lesions in the rectum (78%). Most resections involved the anterior compartment (72%): bladder (n = 13), seminal vesicle/vas deferens (n = 27), ureter (n = 6), prostate (n = 15) and uterus/vagina/adnexa (n = 27). Three cases required conversion to open surgery; 10 patients had grade 3 complications. The median hospital stay was 4 days. Resections were R0 (>1 mm) in 78 and R1 (0 to ≤1 mm) in 8, with none being R2. The average nodal yield was 26 and 48 (55.8%) were pN0. Three-year overall survival was 88% and median progression-free survival was 19.4 months. Local recurrence was 6.1% and distant recurrence was 26.1% at 3 years. CONCLUSION: Performance of multivisceral and extended resection on the robotic platform allows patients the benefit of minimally invasive surgery while achieving oncologically sound resection of colorectal cancer.
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Neoplasias Colorretais , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Procedimentos Cirúrgicos Robóticos/métodos , Feminino , Idoso , Pessoa de Meia-Idade , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Resultado do Tratamento , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Adulto , Estimativa de Kaplan-Meier , Vísceras/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Intervalo Livre de Doença , Tempo de Internação/estatística & dados numéricos , Estudos de Viabilidade , Glândulas Seminais/cirurgiaRESUMO
Importance: Modifier 22 is a mechanism designed for surgeons to identify cases that are more complex than their Current Procedural Terminology code accounts for. However, empirical studies of the use and efficacy of modifier 22 are lacking. Objective: To assess the use of modifier 22 in common surgical procedures and the association of use with compensation. Design, Setting, and Participants: This was a cross-sectional analysis of the 2021 Physician/Supplier Procedure Summary Limited Data Set including all Part B carrier and durable medical equipment fee-for-service claims. Claims for 10 common surgical procedures were evaluated, including mastectomy, total hip arthroplasty, total knee arthroplasty, coronary artery bypass grafting, laparoscopic right colectomy, laparoscopic appendectomy, laparoscopic cholecystectomy, kidney transplant, laparoscopic total abdominal hysterectomy and bilateral salpingo-oophorectomy, and lumbar laminectomy. Data were analyzed from August to November 2023. Main Outcomes and Measures: Rate of modifier 22 use, rate of claim denial, mean charges, mean payment for accepted claims, and mean payment for all claims. Results: The sample included 625â¯316 surgical procedures performed in calendar year 2021. The proportion of modifier 22 coding for a procedure ranged from 5725 of 251â¯521 (2.3%) in total knee arthroplasty to 1566 of 18â¯459 (8.5%) in laparoscopic total abdominal hysterectomy and bilateral salpingo-oophorectomy. Submitted charges were 11.1% (95% CI, 9.1-13.2) to 22.8% (95% CI, 21.3-24.3) higher for claims with modifier 22, depending on the procedure. Among accepted claims, those with modifier 22 had increased payments ranging from 0.8% (95% CI, 0.7-1.0) to 4.8% (95% CI, 4.5-5.1). However, claims with modifier 22 were more likely to be denied (7.4% vs 4.0%; P < .001). As a result, overall mean payments were mixed, with 4 procedures having lower payments when modifier 22 was appended, 4 procedures having higher payments with modifier 22, and 2 procedures with no difference. The largest increase in mean payment for modifier 22 claims was for kidney transplant with an increased payment of $71.46 (95% CI, 55.32-87.60), which translates to a relative increase of 3.4% (95% CI, 2.9-4.6). Conclusions and Relevance: The findings in this study suggest that modifier 22 had little to no financial benefit when appended to claims for a diverse panel of surgical procedures. In the current system, surgeons have little reason to request modifier 22, and no mechanisms currently exist for surgeons to recoup payment for difficult operations.
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Planos de Pagamento por Serviço Prestado , Procedimentos Cirúrgicos Operatórios , Humanos , Estados Unidos , Estudos Transversais , Procedimentos Cirúrgicos Operatórios/economia , Medicare/economia , Feminino , Current Procedural TerminologyRESUMO
BACKGROUND: A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic colorectal cancer (mCRC) was conducted to identify factors used to consider metastasis-directed therapy (MDT). MATERIALS AND METHODS: An online survey to assess clinical factors when weighing MDT in patients with mCRC was developed based on systematic review of the literature and integrated with clinical vignettes. Supporting evidence from the systematic review was included to aid in answering questions. RESULTS: Among 75 experts on mCRC invited, 47 (response rate 62.7%) chose to participate including 16 MOs, 16 ROs, and 15 SOs. Most experts would not consider MDT in patients with 3 lesions in both the liver and lung regardless of distribution or timing of metastatic disease diagnosis (6 vs. 36 months after definitive treatment). Similarly, for patients with retroperitoneal lymph node and lung and liver involvement, most experts would not offer MDT regardless of timing of metastatic disease diagnosis. In general, SOs were willing to consider MDT in patients with more advanced disease, ROs were more willing to offer treatment regardless of metastatic site location, and MOs were the least likely to consider MDT. CONCLUSIONS: Among experts caring for patients with mCRC, significant variation was noted among MOs, ROs, and SOs in the distribution and volume of metastatic disease for which MDT would be considered. This variability highlights differing opinions on management of these patients and underscores the need for well-designed prospective randomized trials to characterize the risks and potential benefits of MDT.
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Neoplasias Colorretais , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Inquéritos e Questionários/estatística & dados numéricos , Oncologistas/estatística & dados numéricos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Metástase Neoplásica , Masculino , Feminino , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Radio-Oncologistas/estatística & dados numéricos , Tomada de Decisão Clínica , Pessoa de Meia-IdadeRESUMO
PURPOSE: Individuals diagnosed with cancer between 15 and 39 years (adolescent and young adult [AYA]) face unique vulnerability. Detail is lacking about care delivery for these patients, especially those with ALL. We address these knowledge gaps by describing AYA ALL care delivery details at National Cancer Institute Community Oncology Research Program (NCORP) (sub)affiliates by model of care. METHODS: Participating institutions treated at least one AYA with ALL from 2012 to 2016. Study-specific criteria were used to determine the number of unique clinical facilities (CFs) per NCORP and their model of care (adult/internal medicine [IM], pediatric, mixed [both]). Surveys completed by NCORPs for each CF by model of care captured size, resources, services, and communication. RESULTS: Among 84 participating CFs (adult/IM, n=47; pediatric, n=15; mixed, n=24), 34% treated 5-10 AYAs with ALL annually; adult/IM CFs more often treated <5 (adult/IM, 60%; pediatric, 40%; mixed, 29%). Referral decisions were commonly driven by an age/diagnosis combination (58%), with frequent ALL-specific age minimums (87%) or maximums (80%). Medical, navigational, and social work services were similar across models while psychology was available at more pediatric CFs (pediatric, 80%; adult/IM, 40%; mixed, 46%-54%). More pediatric or mixed CFs reported oncologists interacting with pediatric/adult counterparts via tumor boards (pediatric, 93%; adult/IM, 26%; mixed, 96%) or initiating contact (pediatric, 100%; adult/IM, 77%; mixed 96%); more pediatric CFs reported an affiliated counterpart (pediatric, 53%; adult, 19%). Most CFs reported no AYA-specific resources (79%) or meetings (83%-98%). CONCLUSION: System-level aspects of AYA ALL care delivery have not been examined previously. At NCORPs, these characteristics differ by models of care. Additional work is ongoing to investigate the impact of these facility-level factors on guideline-concordant care in this population. Together, these findings can inform a system-level intervention for diverse practice settings.
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Neoplasias , Oncologistas , Humanos , Adolescente , Adulto Jovem , Criança , Neoplasias/epidemiologia , Neoplasias/terapia , Neoplasias/diagnóstico , Atenção à Saúde , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The standard treatment for recurrent or persistent anal squamous cell carcinoma is surgical salvage, but disease control and survival are suboptimal. PATIENTS/METHODS: Patients treated for recurrent or persistent anal squamous cell carcinoma at our institution from 2002 to 2022 were included. Patients were classified by type of salvage treatment received: surgery alone vs. reirradiation followed by surgery and by whether they received intraoperative radiation at the time of surgery. Clinical and pathologic variables were collected and assessed for association with risk of second local recurrence and death from any cause. RESULTS: Sixty four patients were included; 55(85.9%) were treated with surgery alone and 9 (14.1%) were treated with reirradiation followed by surgery. Median (IQR) follow up from the time of salvage treatment was 40.0 (20.3-68.0) months. The 3-year cumulative incidence of second local recurrence (95% CI) after salvage surgery was 36% (24%-48%); 39% (26%-52%) for patients treated with surgery alone and 15% (0.46%-51%) for patients treated with reirradiation followed by surgery. Factors associated with increased second local recurrence after salvage surgery included a locoregional recurrence, lymphovascular space invasion and positive surgical margins. The 3-year overall survival (95% CI) after salvage surgery was 70% (59%-83%); 68% (7%-56%) after surgery alone and 89% (10.5%-70.6%) after reirradiation followed by surgery. Factors associated with worse overall survival included male sex, a larger recurrent tumor and positive surgical margins. CONCLUSIONS: Approximately 60% of patients achieved pelvic control after salvage therapy for recurrent or persistent anal squamous cell carcinoma. Although receipt of reirradiation and intraoperative radiation were not associated with improved second local recurrence or overall survival in our cohort, patients with positive surgical margins and lymphovascular space invasion on surgical pathology had higher rates of pelvic recurrence after salvage surgery and may benefit from escalated salvage therapy.
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Neoplasias do Ânus , Carcinoma de Células Escamosas , Humanos , Masculino , Terapia de Salvação , Margens de Excisão , Carcinoma de Células Escamosas/patologia , Neoplasias do Ânus/terapia , Neoplasias do Ânus/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Estudos Retrospectivos , Terapia Combinada , Resultado do TratamentoRESUMO
Cancer stem cells (CSC) play a critical role in metastasis, relapse, and therapy resistance in colorectal cancer. While characterization of the normal lineage of cell development in the intestine has led to the identification of many genes involved in the induction and maintenance of pluripotency, recent studies suggest significant heterogeneity in CSC populations. Moreover, while many canonical colorectal cancer CSC marker genes have been identified, the ability to use these classical markers to annotate stemness at the single-cell level is limited. In this study, we performed single-cell RNA sequencing on a cohort of 6 primary colon, 9 liver metastatic tumors, and 11 normal (nontumor) controls to identify colorectal CSCs at the single-cell level. Finding poor alignment of the 11 genes most used to identify colorectal CSC, we instead extracted a single-cell stemness signature (SCS_sig) that robustly identified "gold-standard" colorectal CSCs that expressed all marker genes. Using this SCS_sig to quantify stemness, we found that while normal epithelial cells show a bimodal distribution, indicating distinct stem and differentiated states, in tumor epithelial cells stemness is a continuum, suggesting greater plasticity in these cells. The SCS_sig score was quite variable between different tumors, reflective of the known transcriptomic heterogeneity of CRC. Notably, patients with higher SCS_sig scores had significantly shorter disease-free survival time after curative intent surgical resection, suggesting stemness is associated with relapse. IMPLICATIONS: This study reveals significant heterogeneity of expression of genes commonly used to identify colorectal CSCs, and identifies a novel stemness signature to identify these cells from scRNA-seq data.
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Neoplasias Colorretais , Recidiva Local de Neoplasia , Humanos , Recidiva Local de Neoplasia/patologia , Perfilação da Expressão Gênica , Neoplasias Colorretais/patologia , Recidiva , Análise de Sequência de RNA , Células-Tronco Neoplásicas/metabolismo , Linhagem Celular TumoralRESUMO
BACKGROUND: Neoadjuvant immune checkpoint blockade (IO) is emerging as a therapeutic option for patients with deficient mismatch repair (dMMR) colorectal cancer (CRC) given high pathological response rates. The aim of the study was to characterise imaging and endoscopic response to IO. METHODS: A retrospective analysis of patients with localised dMMR CRC that received at least one cycle of neoadjuvant anti-PD-1 therapy was conducted. Endoscopy, imaging, and pathological outcomes were reviewed to determine response to treatment according to standardised criteria. RESULTS: Thirty-eight patients had received IO for the treatment of localised CRC (median eight cycles). Among evaluable cases (n = 31 for endoscopy and n = 34 for imaging), the best endoscopic response was complete response (CR) in 45% of cases, and the best radiographic response was CR in 23% of cases. Imaging CR rate after ≤4 cycles of IO (n = 1) was 6% compared to 44% after >4 IO cycles (n = 7). Among 28 patients with imaging and endoscopy available, a discrepancy in best response was noted in 15 (54%) cases. At a median follow-up of 28.2 months from IO start, 18 patients underwent surgical resection of which 11 (61%) had pathological CR (pCR). Despite pCR or no evidence of progression ≥6 months after completion of IO among non-operatively managed patients, 72% and 42% of patients had non-CR on imaging and endoscopy, respectively. CONCLUSIONS: Discrepancies between imaging and endoscopy are prevalent, and irregularities identified on these modalities can be identified despite pathological remission. Improved clinical response criteria are warranted.
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Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Receptor de Morte Celular Programada 1 , Humanos , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA , Endoscopia , Instabilidade de Microssatélites , Terapia Neoadjuvante , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Retrospectivos , Inibidores de Checkpoint Imunológico/uso terapêuticoRESUMO
Importance: Circumferential resection margin (CRM) in rectal cancer surgery is a major prognostic indicator associated with local recurrence and overall survival. Facility rates of CRM positivity have recently been established as a new quality measure by the Commission on Cancer (CoC); however, the completeness of CRM status reporting is not well characterized. Objective: To describe the changes in CRM reporting and factors associated with low rates of reporting. Design, Setting, and Participants: A retrospective cohort study was conducted using data from the National Cancer Database between January 2010 and December 2019. Data were analyzed between October 1, 2021, and February 1, 2022. Data from the National Cancer Database included patients diagnosed with nonmetastatic rectal adenocarcinoma receiving surgical treatment at CoC-accredited facilities throughout the US. Exposures: Patient, tumor, and facility-level factors. Facilities were divided by surgical volume, safety-net status, and CoC facility type. Main Outcomes and Measures: Circumferential resection margin missingness rates. Results: A total of 110â¯571 patients (59.3% men) with rectal adenocarcinoma who underwent curative-intent surgery at 1307 CoC-accredited hospitals were included for analysis. Reporting of CRM improved over the study period, with a mean (SE) missing 12.0% (0.32%) decreased from 16.3% (0.36%). Academic facilities had a higher missingness than other facility types (14.3% vs 10.5%-12.7%; P < .001). Mean (SE) rates of missingness were similar between hospitals of varying volume (lowest quartile: 12.2% [0.93%] vs highest quartile: 12.4% [0.53%]; P = .96). Cases in which fewer than 12 lymph nodes were removed had higher rates of missingness (18.1% vs 11.4%; P < .001). Increased odds of CRM missingness were noted with T category (odds ratio [OR], 1.50; 95% CI, 1.35-1.65) and N category (OR, 2.00; 95% CI, 1.82-2.20). Black race was associated with missingness (OR, 1.13; 95% CI, 1.06-1.14). Conclusion and Relevance: Although CRM positivity reporting has improved over the last decade, the findings of this study suggest there is substantial room for improvement as it becomes a quality standard. Missingness appears to be associated with poor performance on other quality metrics and facility type. This measure appears to be ideal for targeted institution-level feedback to improve quality of care nationally.
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Adenocarcinoma , Neoplasias Retais , Masculino , Humanos , Feminino , Margens de Excisão , Estudos Retrospectivos , Reto/cirurgia , Neoplasias Retais/mortalidade , Adenocarcinoma/mortalidadeRESUMO
The concept of multidisciplinary team discussion of patient's care has been a part of routine medical practice for several decades [Monson et al. in Bull Am Coll Surg 101:45-46, 2016; NHS. Improving outcomes in colorectal cancer-the manual. (Guidance on commissioning cancer services-improving outcomes). 1997.]. The idea of bringing multiple specialties and ancillary services together to help optimize patient outcomes has been implemented in several clinical arenas from burns to physical medicine and rehabilitation to oncology. In the oncology realm, multidisciplinary tumor boards (MDTs) originated as a broad-based meeting that would permit the review and discussion of cancer patients to optimize treatment strategies [Cancer Co. Optimal Resources for Cancer Care: 2020 Standards. Chicago, IL: 2019.]. Over time, as further specialization occurred and clinical treatment algorithms have become more complex, multidisciplinary tumor boards have become more disease site specific. In this article we will discuss the importance of MDTs, specifically focusing on rectal cancer MDTs including their impact on treatment planning as well as the unique interplay of clinical specialties that provide internal quality control and improvement. Additionally, we will discuss some of the potential benefits of MDTs beyond the direct impact on patient care and review some of the challenges of implementation.