Trends in using intraoperative parathyroid hormone monitoring during parathyroidectomy: Protocol and rationale for a cross-sectional survey study of North American surgeons.

Hyperparathyroidism is a common endocrine disorder that occurs secondary to abnormal parathyroid gland functioning. Depending on the type of hyperparathyroidism, surgical extirpation of hyperfunctioning parathyroid glands can be considered for disease cure. Intraoperative parathyroid hormone (IOPTH) monitoring improves outcomes in patients undergoing surgery for primary hyperparathyroidism, but studies are needed to characterize its institutional adoption and its role in surgery for secondary and tertiary hyperparathyroidism, as these entities can be difficult to cure. Hence, we will perform a cross-sectional survey study of surgeon rationale, operational details, and barriers associated with IOPTH monitoring adoption across North America. We will utilize a convenience sampling technique to distribute an online survey to head and neck surgeons and endocrine surgeons across North America. This survey will be distributed via email to three North American professional societies (i.e., Canadian Society for Otolaryngologists-Head and Neck Surgeons, American Head and Neck Society, and American Association of Endocrine Surgeons). The survey will consist of 30 multiple choice questions that are divided into three concepts: (1) participant demographics and training details, (2) details of surgical adjuncts during parathyroidectomy, and (3) barriers to adoption of IOPTH. Descriptive analyses and multiple logistic regression will be used to evaluate the impact of demographic, institutional, and training variables on the use of IOPTH monitoring in surgery for all types of hyperparathyroidism and barriers to IOPTH monitoring adoption. Ethics approval was obtained by the Hamilton Integrated Research Ethics Board (2024-17173-GRA). These findings will characterize surgeon and institutional practices with regards to IOPTH monitoring during parathyroid surgery and will inform future trials aimed to optimize the use of IOPTH monitoring in secondary and tertiary hyperparathyroidism.

Adaptive clinical trials in surgery: A scoping review of methodological and reporting quality.

IMPORTANCE: Adaptive surgical trials are scarce, but adopting these methods may help elevate the quality of surgical research when large-scale RCTs are impractical. OBJECTIVE: Randomized-controlled trials (RCTs) are the gold standard for evidence-based healthcare. Despite an increase in the number of RCTs, the number of surgical trials remains unchanged. Adaptive clinical trials can streamline trial design and time to trial reporting. The advantages identified for ACTs may help to improve the quality of future surgical trials. We present a scoping review of the methodological and reporting quality of adaptive surgical trials. EVIDENCE REVIEW: We performed a search of Ovid, Web of Science, and Cochrane Collaboration for all adaptive surgical RCTs performed from database inception to October 12, 2023. We included any published trials that had at least one surgical arm. All review and abstraction were performed in duplicate. Risk of bias (RoB) was assessed using the RoB 2.0 instrument and reporting quality was evaluated using CONSORT ACE 2020. All results were analyzed using descriptive methods. FINDINGS: Of the 1338 studies identified, six trials met inclusion criteria. Trials were performed in cardiothoracic, oral, orthopedic, and urological surgery. The most common type of adaptive trial was group sequential design with pre-specified interim analyses planned for efficacy, futility, and/or sample size re-estimation. Two trials did use statistical simulations. Our risk of bias evaluation identified a high risk of bias in 50% of included trials. Reporting quality was heterogeneous regarding trial design and outcome assessment and details in relation to randomization and blinding concealment. CONCLUSION AND RELEVANCE: Surgical trialists should consider implementing adaptive components to help improve patient recruitment and reduce trial duration. Reporting of future adaptive trials must adhere to existing CONSORT ACE 2020 guidelines. Future research is needed to optimize standardization of adaptive methods across medicine and surgery.

PReoperative very low-Energy diets for obese PAtients undergoing non-bariatric surgery Randomized Evaluation (PREPARE): a protocol for a pilot randomized controlled trial.

BACKGROUND: Patients with obesity presenting in need of surgical intervention are at 2-to-sixfold higher risk of prolonged hospitalization, infectious morbidity, venous thromboembolism, and more. To mitigate some of these concerns, prescribed preoperative weight loss via very low-energy diets (VLEDs) has become a standard of care for patients with obesity undergoing bariatric surgery. While VLEDs have become standard prior to bariatric surgery, their application in other surgical settings remains limited. A large, definitive trial is required to resolve the uncertainty surrounding their use in these patients. Prior to a definitive trial to compare the efficacy of VLEDs in patients with obesity undergoing major non-bariatric surgery, we require a pilot trial. We argue a pilot trial will provide the following critical feasibility insights: (1) assessment of recruitment ability, (2) evaluation of adherence to VLED regimens, and (3) assessment of our ability follow patients completely. METHODS: The proposed trial will be a multi-center, surgeon, outcome assessor, and data-analyst blinded, parallel pilot randomized controlled trial (RCT). Patients older than 18 years of age with a body mass index (BMI) of greater than 30 kg/m2 undergoing major elective non-bariatric surgery will be eligible for inclusion. Consecutive patients will be allocated 1:1 according to a computer-generated randomization schedule. Randomization will be stratified by center and will employ randomly permutated blocks. All patients in the intervention group will receive standard patient counseling on weight loss and an active VLED protocol. The preoperative VLED protocol will utilize commercially available weight loss products for three weeks preoperatively. The primary outcomes (randomization percentage, recruitment rate, intervention adherence, follow-up completion, network development) will assess feasibility. Descriptive statistics will be used to characterize the study sample. DISCUSSION: The PREPARE pilot RCT will aim to provide feasibility and safety data that will allow for the successful completion of the definitive PREPARE trial that has the potential to provide practice changing data pertaining to the regular use of VLEDs as a means of pre-habilitation for patients with obesity undergoing major non-bariatric surgery. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (reference #NCT05918471) on June 23, 2023.

PREscribing preoperative weight loss prior to major non-bariatric abdominal surgery for patients with Elevated weight: Patient and Provider Survey Protocols (PREPARE surveys).

BACKGROUND: Preoperative very low energy diet (VLED) interventions are used routinely in patients undergoing bariatric surgery, a surgical subspecialty that deals almost exclusively with patients with obesity. Yet, their use and study has been limited in non-bariatric abdominal surgery. To investigate the use of VLEDs in non-bariatric surgery, we plan on conducting a randomized controlled trial (RCT). Prior to proceeding, however, we have designed two surveys as important pre-emptive studies aimed at elucidating patient and provider perspectives regarding these interventions. METHODS: The patient survey is a cross-sectional, single-center survey aimed at assessing the safety, adherence, barriers to adherence, and willingness to participate in preoperative optimization protocols with VLEDs prior to undergoing elective non-bariatric intra-abdominal surgery (S1 File). The population of interest is all adult patients with obesity undergoing elective non-bariatric intra-abdominal surgery at St. Joseph's Healthcare Hamilton who were prescribed a course of preoperative VLED. The primary outcomes will be safety and adherence. The target sample size is 35 survey responses. The provider survey is a cross-sectional national survey of practicing surgeons in Canada who perform major non-bariatric abdominal surgery aimed assessing the willingness and ability to prescribe preoperative weight loss interventions amongst practicing Canadian surgeons who perform major non-bariatric abdominal surgery (S2 File). The population of interest is independent practicing surgeons in Canada who perform major non-bariatric abdominal surgery. The primary outcome will be willingness to prescribe preoperative VLED to patients with obesity undergoing major non-bariatric abdominal surgery for both benign and malignant indications. The target sample size is 61 survey responses. Descriptive statistics will be used to characterize the sample populations. To determine variables associated with primary outcomes in the surveys, regression analyses will be performed. DISCUSSION: These survey data will ultimately inform the design of an RCT evaluating the efficacy of preoperative VLEDs for patients with obesity undergoing major abdominal surgery.

REporting quality of PilOt randomised controlled trials in surgery (REPORTS): a methodological survey protocol.

INTRODUCTION: The aim of this methodological review is to evaluate the completeness of reporting of surgical pilot and feasibility randomised trials as per the Consolidated Standards of Reporting Trials (CONSORT) extension to randomised pilot and feasibility trials. Moreover, we aim to assess for the presence of spin reporting and inconsistency between abstract and main text reporting in surgical pilot and feasibility randomised trials. METHODS AND ANALYSIS: A comprehensive, electronic search strategy will be used to identify studies indexed in Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Studies will be included if they are pilot or feasibility randomised trials of surgical interventions. The primary outcome will be overall CONSORT statement extension to randomised pilot and feasibility trials checklist completeness. This will be defined as trials reporting each of the 40 items in the CONSORT statement extension to randomised pilot and feasibility trials checklist. Secondary outcomes will include the reporting of individual studies as per the CONSORT extension to randomised pilot and feasibility trials, the use of spin reporting strategies, trial factors associated with reporting quality and spin strategy use, and consistency between abstract and main text reporting. Poisson and logistic regressions will be performed to explore the association between trial factors and completeness of reporting as measured by the number of reported CONSORT items. ETHICS AND DISSEMINATION: This is a methodological survey that has been registered a priori on the International Prospective Register for Systematic Reviews (PROSPERO) (CRD42023475512). Local ethics approval is not required. We plan to disseminate study results through peer-reviewed publication and conference presentations.

Pilot and feasibility trials in surgery are incompletely reported according to the CONSORT checklist: a meta-research study.

OBJECTIVES: Given the key role that pilot and feasibility (PAF) trials play in addressing the challenges of surgical trials, adequate reporting completeness is essential. Our aim was to assess completeness of reporting and evaluate if the items of the Consolidated Standards of Reporting Trials (CONSORT) extension for PAF trials have been reported in surgical PAF trials. STUDY DESIGN: This is a metaresearch study reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were included if they were pilot or feasibility randomized trials evaluating a surgical intervention. The primary outcome was overall adherence to the CONSORT statement extension to randomized PAF trials checklist. A Poisson regression was performed to explore the association between research factors and reporting completeness. SETTING: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched from January 1-December 31, 2011 and 2021. RESULTS: After screening 1991 citations, 38 studies from 2011 to 34 studies from 2021 were included. The mean CONSORT reporting score across all included studies was 21.5 (standard deviation 6.3). After excluding items that were not applicable to all studies, a mean of 20.1 (standard deviation 6.1) of 34 items (0.59) were reported. Studies published in 2021 (vs 2011) did not have a greater number of CONSORT items reported (incidence rate ratio [IRR] 1.01, 95% confidence interval [CI] 0.89-1.15). Studies registered in a clinical trial registry (IRR 1.29, 95% CI 1.12-1.48) and randomizing more than 50 patients (IRR 1.16, 95% CI 1.04-1.30) were associated with more CONSORT items reported. CONCLUSION: The reporting completeness of surgical PAF trials is poor and has not improved after the publication of the CONSORT extension.

LUMINA: Using molecular biomarkers to guide decision making for breast radiotherapy.

In this opinion piece, we respond to comments about the LUMINA trial by Meattini and colleagues in the Journal. LUMINA was a prospective cohort study which evaluated the omission of radiotherapy after breast conserving surgery (BCS) in patients treated with endocrine therapy with low risk clinico-pathologic features and luminal A breast cancer. We address their areas of concern including the single cohort design that required careful patient selection, the relatively short follow-up period of 5 years, and the limited follow-up on younger patients. The Ki67 biomarker was key to defining the luminal A phenotype. We clarify the evidence supporting the Ki67 criteria used. The compliance with endocrine therapy was high and similar to other contemporary trials. Based on the results of LUMINA, and mounting evidence from other trials, we feel comfortable offering our patients the option of no radiotherapy after BCS if they fit the trial eligibility criteria from LUMINA and have decided to receive adjuvant endocrine therapy. We concur that a patient-centered approach to treatment decision making should be used to make patients aware of all available information including the results of the LUMINA trial when deciding on post-operative breast radiotherapy.

The impact of operative approach for obese colorectal cancer patients: analysis of the National Inpatient Sample 2015-2019.

AIM: Obesity is a well-established risk factor for the development of colorectal cancer. As such, patients undergoing surgery for colorectal cancer have increasingly higher body mass indices (BMIs). The advances in minimally invasive surgical techniques in recent years have helped surgeons circumvent some of the challenges associated with operating in the setting of obesity. While previous studies suggest that laparoscopy improves outcomes compared with open surgery in obese patients, this has never been established at the population level. Therefore, we designed a retrospective database study using the National Inpatient Sample (NIS) with the aim of comparing laparoscopic with open approaches for obese patients undergoing surgery for colorectal cancer. METHOD: A retrospective analysis of the NIS from 2015 to 2019 was conducted including patients with a BMI of greater than 30 kg/m2 undergoing surgery for colorectal cancer. The primary outcomes were postoperative in-hospital morbidity and mortality. Secondary outcomes included postoperative system-specific complications, total admission healthcare cost and length of stay (LOS). Multivariable logistic and linear regressions were utilized to compare the two operative approaches. RESULTS: A total of 4742 patients underwent open surgery and 3231 underwent laparoscopic surgery. We observed a significant decrease in overall postoperative morbidity [17.5% vs. 31.4%, adjusted odds ratio (aOR) 0.56, 95% confidence interval (CI) 0.50-0.64; p < 0.001], gastrointestinal morbidity (8.1% vs. 14.5%, aOR 0.59, 95% CI 0.50-0.69; p < 0.001) and genitourinary morbidity (10.1% vs. 18.6%, aOR 0.61, 95% CI 0.52-0.70; p < 0.001) with the use of laparoscopy. Postoperative LOS was 1.7 days shorter (95% CI 1.5-2.0, p < 0.001) and cost of admission was decreased by $9106 (95% CI $4638-$13 573, p < 0.001) with laparoscopy. CONCLUSION: Laparoscopic surgery for obese patients with colorectal cancer is associated with significantly decreased postoperative morbidity and improved healthcare resource utilization compared with open surgery. Laparoscopic approaches should be relied upon whenever feasible for these patients.

Enhanced recovery after surgery protocols following emergency intra-abdominal surgery: a systematic review and meta-analysis.

PURPOSE: The aim of this systematic review and meta-analysis was to evaluate whether Enhanced Recovery After Surgery (ERAS) protocols for patients undergoing emergency intra-abdominal surgery improve postoperative outcomes as compared to conventional care. METHODS: MEDLINE, EMBASE, WoS, CENTRAL, and Pubmed were searched from inception to December 2022. Articles were eligible if they were randomized controlled trials (RCT) or non-randomized studies comparing ERAS protocols to conventional care for patients undergoing emergency intra-abdominal surgery. The outcomes included postoperative length of stay (LOS), postoperative morbidity, prolonged postoperative ileus (PPOI), and readmission. An inverse variance random effects meta-analysis was performed. A risk of bias was assessed with Cochrane tools. Certainty of evidence was assessed with GRADE. RESULTS: After screening 1018 citations, 20 studies with 1615 patients in ERAS programs and 1933 patients receiving conventional care were included. There was a reduction in postoperative LOS in the ERAS group for patients undergoing upper gastrointestinal (GI) surgery (MD3.35, 95% CI 2.52-4.17, p < 0.00001) and lower GI surgery (MD2.80, 95% CI 2.62-2.99, p < 0.00001). There was a reduction in postoperative morbidity in the ERAS group for patients undergoing upper GI surgery (RR0.56, 95% CI 0.30-1.02, p = 0.06) and lower GI surgery (RR 0.66, 95%CI 0.52-0.85, p = 0.001). In the upper and lower GI subgroup, there were nonsignificant reductions in PPOI in the ERAS groups (RR0.59, 95% CI 0.30-1.17, p = 0.13; RR0.49, 95% CI 0.21-1.14, p = 0.10). There was a nonsignificant increased risk of readmission in the ERAS group (RR1.60, 95% CI 0.57-4.50, p = 0.50). CONCLUSION: There is low-to-very-low certainty evidence supporting the use ERAS protocols for patients undergoing emergency intra-abdominal surgery. The currently available data are limited by imprecision.

A history of bariatric surgery before surgery for colorectal cancer may improve short-term postoperative outcomes: Analysis of the national inpatient sample 2015-2019.

BACKGROUND: Bariatric surgery is the most effective and sustainable form of weight loss. Bariatric surgery before elective operations for colorectal pathology may improve postoperative outcomes. To compare patients with and without prior bariatric surgery undergoing surgery for colorectal cancer in terms of postoperative morbidity and health care use. METHODS: Adult patients undergoing resection for colorectal cancer from 2015 to 2019 were identified from the National Inpatient Sample. Patients were stratified according to their history of bariatric surgery. Propensity score matching with 4:1 nearest-neighbor matching was performed according to demographic, operative, and hospital characteristics. The primary outcome was postoperative morbidity. Secondary outcomes included system-specific postoperative complications, postoperative mortality, postoperative length of stay, total admission health care cost, and post-discharge disposition. McNemar's test and Wilcoxon matched-pairs signed-rank test were performed. RESULTS: After propensity score matching, 1,197 patients without prior bariatric surgery and 376 patients with prior bariatric surgery were included. Patients with prior bariatric surgery had an absolute reduction of 6.5% in overall in-hospital postoperative morbidity (19.1% vs 25.6%, P < .0001), a $5,256 decrease in hospitalization cost ($70,344 vs $75,600, P = .034), and were more likely to be discharged home after their index operation (72.9% vs 63.9%, P < .0001). CONCLUSION: Bariatric surgery before surgery for colorectal cancer may be associated with decreased postoperative morbidity and health care use. Bariatric surgery and other forms of rapid and effective weight loss, such as very low-energy diets, should be evaluated further for the optimization of obese patients before nonbariatric abdominal surgery.

Enhanced Recovery After Surgery (ERAS) protocols following emergency intra-abdominal surgery: A systematic review and meta-analysis protocol.

OBJECTIVE: The aim of this systematic review and meta-analysis is to evaluate whether the implementation of Enhanced Recovery After Surgery (ERAS) protocols for adult patients undergoing emergency intra-abdominal surgery decreases postoperative length of stay, postoperative morbidity, and mortality compared to conventional perioperative care. METHODS: A systematic review and meta-analysis will be performed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). It has been registered on the International Prospective Register for Systematic Reviews (PROSPERO; CRD42023391709). A comprehensive, electronic search strategy will be used to identify studies published and indexed in MEDLINE, EMBASE, Web of Science, CENTRAL, and Pubmed databases since their inception. Trial registries and references of included studies and pertinent previous systematic reviews will also be searched. Studies will be included if they are randomized controlled trials or cohort studies evaluating adult patients undergoing emergency intra-abdominal surgery and comparing ERAS or modified ERAS protocols to conventional perioperative care and report one of the following outcomes: postoperative length of stay, overall 30-day morbidity, 30-day mortality, 30-day infectious morbidity, prolonged postoperative ileus, return of bowel function, and 30-day readmissions. A meta-analysis will be performed using a random effects model for all comparative data using Cochrane Review Manager 5.3 (London, United Kingdom). DISCUSSION: ERAS protocols have become standard of care for patients undergoing elective surgery. Their use in the setting of emergency surgery is far less common. The aim of this systematic review and meta-analysis is to assess whether there are benefits in patient important outcomes with the implementation of ERAS protocols for patients undergoing emergency intra-abdominal surgery. Ultimately, we hope to promote their use and further large randomized controlled trials evaluating emergency surgery ERAS programs. PROSPERO REGISTRATION NUMBER: CRD42023391709.

Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer.

BACKGROUND: Adjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects. Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information. METHODS: We performed a prospective cohort study involving women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A-subtype breast cancer (defined as estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%), and had received adjuvant endocrine therapy. Patients who met the clinical eligibility criteria were registered, and Ki67 immunohistochemical analysis was performed centrally. Patients with a Ki67 index of 13.25% or less were enrolled and did not receive radiotherapy. The primary outcome was local recurrence in the ipsilateral breast. In consultation with radiation oncologists and patients with breast cancer, we determined that if the upper boundary of the two-sided 90% confidence interval for the cumulative incidence at 5 years was less than 5%, this would represent an acceptable risk of local recurrence at 5 years. RESULTS: Of 740 registered patients, 500 eligible patients were enrolled. At 5 years after enrollment, recurrence was reported in 2.3% of the patients (90% confidence interval [CI], 1.3 to 3.8; 95% CI, 1.2 to 4.1), a result that met the prespecified boundary. Breast cancer occurred in the contralateral breast in 1.9% of the patients (90% CI, 1.1 to 3.2), and recurrence of any type was observed in 2.7% (90% CI, 1.6 to 4.1). CONCLUSIONS: Among women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at 5 years was low with the omission of radiotherapy. (Funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation; LUMINA ClinicalTrials.gov number, NCT01791829.).

Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis.

AIMS: Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations. METHODS AND RESULTS: An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10. Discrimination (c-statistic with 95% confidence intervals [CI] and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was subsequently compared with algorithms based on the Wells score and D-dimer testing. The final model included age (in years), sex, previous VTE, recent surgery or immobilization, haemoptysis, cancer, clinical signs of deep vein thrombosis, inpatient status, D-dimer (in µg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95% CI, 0.85-0.89; 95% PI, 0.77-0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87-1.14; 95% PI, 0.55-1.79). The model slightly overestimated VTE probability in the lower range of estimated probabilities. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c-statistic 0.73; 95% CI, 0.70-0.75) or structured clinical pretest probability (c-statistic 0.79; 95% CI, 0.76-0.81). CONCLUSION: The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study. REGISTRATION: PROSPERO ID 89366.

Very low energy diets prior to bariatric surgery may reduce postoperative morbidity: a systematic review and meta-analysis of randomized controlled trials.

Purpose: To optimize patients prior to bariatric surgery, very low energy diets (VLEDs) are often employed for 2-4 weeks preoperatively. They are known to result in preoperative weight loss, decrease liver volume, and decrease surgeon-perceived operative difficulty. Their impact on postoperative morbidity has been less extensively studied. We performed a focused systematic review and meta-analysis with the aim of comparing preoperative VLEDs prior to bariatric surgery with controls in terms of overall postoperative morbidity. Methods: MEDLINE, Embase, and CENTRAL were searched from database inception to February 2023. Articles were eligible for inclusion if they were randomized controlled trials (RCTs) comparing postoperative morbidity in adult patients (i.e., over the age of 18) receiving a VLED with liquid formulation to those receiving a non-VLED control prior to elective bariatric surgery. Outcomes included overall 30-day postoperative morbidity and preoperative weight loss. An inverse variance meta-analysis was performed with GRADE assessment of the quality of evidence. Results: After reviewing 2,525 citations, four RCTs with 294 patients receiving preoperative VLEDs with liquid formulation and 294 patients receiving a non-VLED control met inclusion. Patients receiving VLED experienced significantly more preoperative weight loss than patients receiving control (mean difference (MD) 3.38 kg, 95% confidence interval (CI) 1.06-5.70, p = 0.004, I2 = 95%). According to low certainty evidence, there was a non-significant reduction in 30-day postoperative morbidity in patients receiving VLED prior to bariatric surgery (risk ratio (RR) 0.67, 95%CI 0.39-1.17, p = 0.16, I2 = 0%). Conclusion: The impact of preoperative VLEDs on postoperative outcomes following bariatric surgery remains unclear. It is possible that VLEDs may contribute to decreased postoperative morbidity, but further larger prospective trials are required to investigate the signal identified in this study.

Impact of 18F-Labeled Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Versus Conventional Staging in Patients With Locally Advanced Breast Cancer.

PURPOSE: Patients with locally advanced breast cancer (LABC) typically undergo staging tests at presentation. If staging does not detect metastases, treatment consists of curative intent combined modality therapy (neoadjuvant chemotherapy, surgery, and regional radiation). Positron emission tomography-computed tomography (PET-CT) may detect more asymptomatic distant metastases, but the evidence is based on uncontrolled studies. METHODS: For inclusion, patients had histological evidence of invasive ductal carcinoma of the breast and TNM stage III or IIb (T3N0, but not T2N1). Consenting patients from six regional cancer centers in Ontario were randomly assigned to 18F-labeled fluorodeoxyglucose PET-CT or conventional staging (bone scan, CT of the chest/abdomen and pelvis). The primary end point was upstaging to stage IV. A key secondary outcome was receiving curative intent combined modality therapy (ClinicalTrials.gov identifier: NCT02751710). RESULTS: Between December 2016 and April 2022, 184 patients were randomly assigned to whole-body PET-CT and 185 patients to conventional staging. Forty-three (23%) PET-CT patients were upstaged to stage IV compared with 21 (11%) conventional staged patients (absolute difference, 12.3% [95% CI, 3.9 to 19.9]; P = .002). Consequently, treatment was changed in 35 (81.3%) of 43 upstaged PET-CT patients and 20 (95.2%) of the 21 upstaged conventional patients. Subsequently, 149 (81%) patients in the PET-CT group received combined modality treatment versus 165 (89.2%) patients in the conventional staging group (absolute difference, 8.2% [95% CI, 0.1 to 15.4]; P = .03). CONCLUSION: In patients with LABC, PET-CT detected more distant metastases than conventional staging, and fewer PET-CT patients received combined modality therapy. Our randomized trial demonstrates the utility of the PET-CT staging strategy.

Long-term outcomes and effects of hypofractionated radiotherapy in microinvasive breast cancer: Analysis from a randomized trial.

PURPOSE: The natural history of microinvasive (T1mi) breast cancer is uncertain. The objective was to evaluate long-term local and distant recurrence rates following breast conserving surgery (BCS) in a prospective cohort of patients with T1mi compared to T1a-2 disease who received whole breast irradiation (WBI) in the context of a randomized trial of hypofractionation. METHODS: 1234 patients with T1-2 N0 breast cancer were randomized to receive adjuvant WBI of 42.5Gy in 16 daily fractions, or 50Gy in 25 daily fractions after BCS. An analysis of patients with T1mi tumors compared with T1a-2 disease was performed. Kaplan-Meier estimates of local recurrence (LR), distant recurrence, and overall survival (OS) were compared using the log-rank test. RESULTS: Median follow-up was 12 years. T1mi was found in 3% (n = 38) of patients. The 10-year LR rate was 22.6% in T1mi vs. 6.9% in T1a-2 breast cancer [hazard ratio (HR) = 3.73; 95% confidence interval (CI): 1.93, 7.19; p < 0.001]. The 10-year risk of distant recurrence was 5.1% for T1mi, and 12.1% for T1a-2 disease (HR = 0.56; 95% CI: 0.19, 1.84; p = 0.36). Ten-year OS was 91.5% in T1mi and 84.4% in T1a-2 disease, (HR = 0.48; 95% CI: 0.18, 1.30; p = 0.14). Rates of LR did not differ whether treated by hypofractionation or conventional fractionation (HR = 1.21; 95% CI: 0.35, 4.18; p = 0.77). CONCLUSIONS: The risk of LR was considerably higher in patients with T1mi compared to T1a-2 tumors, but OS remained very good. Future research should evaluate the utility of wider local excision and boost radiation to optimize local control for microinvasive breast cancer.

Use of population-based electronic databases for the identification of patients with synchronous colorectal cancer and liver metastases potentially eligible for a surgical trial.

BACKGROUND: Some population-based recruitment methods, such as registries and databases, have been used to increase enrolment in clinical trials by identifying eligible participants based on baseline characteristics; however; these methods have not been tested in surgical trials, in which accrual occurs before surgery. We evaluated the use of population-based electronic databases to identify patients who potentially could be accrued to the Simultaneous Resection of Colorectal Cancer with Synchronous Liver Metastases (RESECT) trial and compared it to the traditional methods used to accrue patients (e.g., multidisciplinary rounds, letters to community surgeons) for that same trial during the same period. METHODS: An electronic database (ePath) was interrogated every 2 weeks for patients diagnosed with colorectal cancer from Feb. 1, 2017, to Mar. 30, 2019. A radiologic image database (OneView) was reviewed to identify those with liver metastases (level 1 screening). Reports were interrogated to identify potentially eligible patients for the RESECT trial (level 2 screening). A hepatobiliary surgeon reviewed radiology images to identify eligible patients for the trial (level 3 screening). The primary outcome was patient eligibility for the ongoing RESECT trial. RESULTS: The population-based method identified 90 (11.2%) of 803 patients diagnosed with colorectal cancer over the study period. Among the 90 patients, level 2 screening identified 60 (67%) potentially eligible patients for the RESECT trial. Of the 90 patients, 18 (20%) were eligible after radiographic image review (level 3 screening). Traditional accrual methods identified 38 patients with liver metastases, 27 (71%) of whom were identified as potentially eligible on level 2 screening, and 14 (37%) of whom were deemed to be eligible on level 3 screening. Twenty-six patients were identified by both methods. Twelve patients were identified by population-based methods alone, and 8 patients by traditional methods alone. Six eligible patients were identified by both methods. Baseline characteristics were similar between the 2 groups. CONCLUSION: A population-based electronic database method of patient accrual was able to identify eligible participants for the RESECT trial. However, optimal accrual likely requires the use of traditional methods as well.

Low-Dose Hemibody Radiation, a Treatment Option for Recurrent Prostate Cancer: A Phase 2 Single-Arm Trial.

Purpose: Nontargeted low-dose ionizing radiation has been proposed as a cancer therapeutic for several decades; however, questions remain about the duration of hematological changes and optimal dosing regimen. Early studies delivering fractionated low doses of radiation to patients with cancer used varying doses and schedules, which make it difficult to standardize a successful dose and scheduling system for widespread use. The aim of this phase 2 two-stage trial was to determine whether low-dose radiation therapy (LD-RT) reduced prostate-specific antigen (PSA) in patients with recurrent prostate cancer in efforts to delay initiation of conventional therapies that are known to decrease quality of life. The primary study outcome was reduction in PSA levels by at least 50%. Methods and Materials: Sixteen patients with recurrent prostate cancer were recruited and received 2 doses of 150 mGy of nontargeted radiation per week, for 5 consecutive weeks, with 15 participants completing the study. Results: A maximal response of 40.5% decrease in PSA at 3 months was observed. A total of 8 participants remained off any additional interventions, of whom 3 had minor fluctuations in PSA for at least 1 year after treatment. The most common adverse event reported was mild fatigue during active treatment (n = 4), which did not persist in the follow-up period. No participants withdrew due to safety concerns or hematological abnormalities (ie, platelet ≤50 × 109/L, leukocyte ≤3 × 109/L, granulocyte ≤2 × 109/L). Conclusions: Our study did not meet the primary objective; however, LD-RT may be a potential therapy for some patients with recurrent prostate cancer by stalling rising PSA. This study also demonstrates that low-dose radiation is well tolerated by participants with minimal toxicities and no change in quality of life.

Lung SBRT credentialing in the Canadian OCOG-LUSTRE randomized trial.

Purpose: To report on the Stereotactic Body Radiation Therapy (SBRT) credentialing experience during the Phase III Ontario Clinical Oncology Group (OCOG) LUSTRE trial for stage I non-small cell lung cancer. Methods: Three credentialing requirements were required in this process: (a) An institutional technical survey; (b) IROC (Imaging and Radiation Oncology Core) thoracic phantom end-to-end test; and (c) Contouring and completion of standardized test cases using SBRT for one central and one peripheral lung cancer, compared against the host institution as the standard. The main hypotheses were that unacceptable variation would exist particularly in OAR definition across all centres, and that institutions with limited experience in SBRT would be more likely to violate per-protocol guidelines. Results: Fifteen Canadian centres participated of which 8 were new, and 7 were previously established (≥2 years SBRT experience), and all successfully completed surveys and IROC phantom testing. Of 30 SBRT test plans, 10 required replanning due to major deviations, with no differences in violations between new and established centres (p = 0.61). Mean contouring errors were highest for brachial plexus in the central (C) case (12.55 ± 6.62 mm), and vessels in the peripheral (P) case (13.01 ± 12.55 mm), with the proximal bronchial tree (PBT) (2.82 ± 0.78 C, 3.27 ± 1.06 P) as another variable structure. Mean dice coefficients were lowest for plexus (0.37 ± 0.2 C, 0.37 ± 0.14 P), PBT (0.77 ± 0.06 C, 0.75 ± 0.09 P), vessels (0.69 ± 0.29 C, 0.64 ± 0.31 P), and esophagus (0.74 ± 0.04 C, 0.76 ± 0.04 P). All plans passed per-protocol planning target volume (PTV) coverage and maximum/volumetric organs-at-risk constraints, although variations existed in dose gradients within and outside the target. Conclusions: Clear differences exist in both contouring and planning with lung SBRT, regardless of centre experience. Such an exercise is important for studies that rely on high precision radiotherapy, and to ensure that implications on trial quality and outcomes are as optimal as possible.