Longitudinal Links between Changes in Body Composition and Liver Disease Severity in Children and Adolescents with Metabolic Dysfunction-Associated Steatotic Liver Disease.

OBJECTIVE: To investigate the relationship between longitudinal changes in body composition and liver disease severity in children with metabolic dysfunction-associated steatotic liver disease (MASLD). STUDY DESIGN: This longitudinal, single-center, retrospective analysis included patients aged <20 years followed for MASLD who had had ≥2 bioelectrical impedance analyses (BIAs) performed. MASLD regression was defined as alanine aminotransferase (ALT) normalization or a decrease of >50% from baseline. Fat and skeletal muscle mass were adjusted for size by calculating respective indices (dividing by height2). Logistic and linear regressions were used to determine the independent relationship between changes in body composition over time and serological markers of liver disease severity. RESULTS: We included 258 patients (75% male, 50% Hispanic) with a median age of 14 years (IQR, 11-16 years) at the time of first BIA. Median body mass index (BMI) z-score at baseline was 2.33 (IQR, 2.04-2.62). Median time from first to last BIA was 12 months (IQR, 6-24 months). A decrease in fat mass index was independently associated with reductions in ALT and gamma glutamyl transferase and increased odds of MASLD regression (OR; 0.55; P < .001). Fat mass index reduction was superior to BMI z-score in predicting MASLD regression. Change in skeletal muscle mass index was not associated with change in ALT or gamma glutamyl transferase. CONCLUSIONS: Changes in fat mass, not skeletal muscle mass, are associated with serological markers of liver injury in youth with MASLD. Fat mass changes outperform BMI z-score changes in predicting MASLD regression. BIA can serve as an adjunct biomarker of liver disease progression.

Alliance for clinical trials in Oncology (Alliance) trial A022101/NRG-GI009: a pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur).

BACKGROUND: For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. METHODS: The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. DISCUSSION: The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05673148, registered December 21, 2022.

A phase II study of neoadjuvant liposomal irinotecan with 5-FU and oxaliplatin (NALIRIFOX) in pancreatic adenocarcinoma.

For patients with localized pancreatic cancer with minimal vascular involvement, optimal survivability requires a multidisciplinary approach of surgical resection and systemic chemotherapy. FOLFIRINOX is a combination chemotherapy regimen that offers promising results in the perioperative and metastatic settings; however, it can cause significant adverse effects. Such toxicity can negatively impact some patients, resulting in chemotherapy discontinuation or surgical unsuitability. In an effort to reduce toxicities and optimize outcomes, this investigation explores the safety and feasibility of substituting liposomal irinotecan (nal-IRI) for nonliposomal irinotecan to improve tumor drug delivery and potentially reduce toxicity. This regimen, NALIRIFOX, has the potential to be both safer and more effective when administered in the preoperative setting.

For patients with pancreatic cancer with little to no cancer near the blood vessels, the best life expectancy usually requires surgery and chemotherapy. FOLFIRINOX is a chemotherapy medicine that offers promising results for both patients getting surgery and for patients with widespread disease. However, it can cause harmful side effects. The side effects can be so bad that the chemotherapy has to be stopped or that surgery is no longer possible. In order to reduce the harmful side effects and improve outcomes, this investigation looks into the safety and practicality of using a different version of one of the medicines. The different version hopes to improve drug delivery and reduce harmful side effects. This regimen, NALIRIFOX, can be safer and more effective in patients awaiting surgery. Clinical Trial Registration: UF-STO-PANC-004 (NCT03483038) (ClinicalTrials.gov).

National adoption of neoadjuvant chemotherapy: paradigm shift in the treatment of pancreatic cancer.

BACKGROUND: The historical standard of care in treating operable pancreatic cancer via upfront surgery has been challenged recently using a neoadjuvant approach. The aim of the study is to examine the national practice patterns in the management of pancreatic cancer with an emphasis on the trends of neoadjuvant systemic therapy use. METHODS: This is a cross-sectional time-series study using the National Cancer Database from 2006 to 2019. Patients who underwent resection for stage I-II pancreatic adenocarcinoma were selected. RESULTS: Overall, 25% of patients had neoadjuvant chemotherapy, 49% had surgery followed by adjuvant chemotherapy and 26% had surgery alone. The rate of neoadjuvant chemotherapy has increased from 11% in 2006 to 43% in 2019. There was a decrease in the rate of surgery followed by chemotherapy from 48% to 38%, and a decrease in the rate of surgery alone from 41% to 19%. The rate of radiation therapy use has decreased over time, as has the resection rate, while median overall survival has steadily improved over the years. CONCLUSIONS: In 2019, the rate of using neoadjuvant systemic therapy overtook the rate of surgery first followed by adjuvant systemic therapy, marking a pragmatic national shift in the clinical management of pancreatic cancer.

Woody hardness classification impact on salvage laryngectomy functional outcomes.

PURPOSE: Post-radiation therapy salvage surgeries are challenging for surgeons due to tissue fibrosis. The woody hardness classification is valuable in differentiating the degree of neck stiffness, but its clinical utility has not been evaluated. We applied it to patients undergoing salvage laryngectomy to study the impact of woody hardness on postoperative outcomes. MATERIALS AND METHODS: A retrospective observational study was performed on patients undergoing salvage laryngectomy between 2014 and 2019. Patients were assigned into the A (extremely woody hard), B (moderately woody hard), or C (mildly woody hard) woody hardness class. The primary outcome was pharyngoesophageal stricture development. Secondary outcomes included time to pharyngoesophageal stricture, pharyngocutaneous fistula development, time to pharyngocutaneous fistula, development of post-operative complications, and tracheoesophageal puncture complications. RESULTS: Fifty-one patients were included in the study: Class A 1 patient, Class B 30 patients, and Class C 20 patients. The single Class A patient was grouped with the Class B patients. The development of a pharyngoesophageal stricture shows consistent negative association with woody hardness despite most analyses not reaching statistical significance. These associations are robust to a number of confounding variables in multivariate logistic and time to event analyses. Furthermore, the time to event analysis controlling for squamous cell carcinoma diagnosis led to a statistically significant association between woody hardness (i.e., A/B higher risk) and time to stricture (HR=5, p=0.02). CONCLUSIONS: This study suggests that this classification may be useful in predicting pharyngoesophageal stricture formation in salvage laryngectomy patients and could be used to implement stricture preventive measures.

HPV/p16-positive oropharyngeal cancer treated with transoral robotic surgery: The roles of margins, extra-nodal extension and adjuvant treatment.

PURPOSE: Human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) treatment outcomes are re-defining management. Traditional margins, the role of extranodal extension (ENE) and adjuvant treatment intensity continue to be debated. This study aimed to determine the impact of margins, ENE and adjuvant therapy on survival following transoral robotic surgery (TORS). METHODS: Patients treated with TORS at an academic center were retrospectively identified (2013-2019). Survival outcomes were evaluated using Kaplan-Meier curves. RESULTS: 48 patients were included. 40 (83%) were male. Mean age was 61.2 years. 43 (90%) were stage I. 22 (45.8%) had ENE. 31 (65%) had margins >1 mm. 38 (79%) had indications for radiation therapy; 9 (24%) refused. Chemotherapy was recommended in 36 (75%) patients; 24 (67%) refused. Locoregional control was 98%, metastasis-free survival was 96%, and disease-specific survival was 100% at 5-years. Overall survival was 95%. CONCLUSIONS: Given the high survival rate seen after TORS, it is likely that margins, ENE and adjuvant treatment may not significantly contribute to outcomes.

Role of irradiation for patients over 80 years old with glioblastoma: a retrospective cohort study.

To assess efficacy and safety of hypofractionated radiation therapy (HRT) in patients over 80 years old with newly diagnosed glioblastoma (GBM). Between June 2009 and September 2015, patients in this population with a recommendation for radiation therapy from a multidisciplinary tumor board, and a Karnofsky performance status (KPS) ≥60 as assessed by a radiation oncologist, who received HRT (40 Gy/15 fractions) ± concomitant and adjuvant temozolomide (TMZ) were retrospectively analyzed. A total of 21 patients fulfilled the criteria for eligibility. Median KPS was 80 (60-90). After a median follow-up of 5.8 months (IQR 3.7-13.1 months), median overall survival (OS) was 7.5 months (95 % CI 4.5-19.1) and the 1-year and 2-year OS were 39.5 % (95 % CI 21.9-71.2 %) and 6.6 % (95 % CI 1.0- 43.3 %), respectively. Median progression-free survival (PFS) was 5.8 months (95 % CI 3.9-7.7 months), 1-year and 2-year PFS were 15.2 % (95 % CI 4.4-52.4) and 0 %, respectively. Overall, 16 (76.2 %) patients presented a recurrence. Overall seven patients (33.3 %) needed to be hospitalized during treatment. On univariate analysis, hospitalization was the only variable that correlated with less favourable outcome in terms of both OS (12.2 months versus 3.8 months, p < 0.010) and PFS (5.8 months versus 3.4 months, p = 0.002). Our study suggests that HRT is feasible with acceptable tolerance among "very elderly" patients affected by GBM. Patients 80 and older should be considered for management based on RT.

Retromolar trigone squamous cell carcinoma treated with radiotherapy alone or combined with surgery: a 10-year update.

PURPOSE/OBJECTIVES: Treatment outcomes were analyzed for patients who received radiotherapy for squamous cell carcinoma of the retromolar trigone at a single institution. MATERIALS/METHODS: We reviewed the medical records of 110 patients treated with radiotherapy alone (n=36) or radiotherapy combined with surgical resection of the primary tumor (n=74) between June 1966 and October 2013. The median follow-up was 4.5years for all patients and 11.8years for living patients (range, 1.3-23.5years). RESULTS: The 5-year local-regional control rates after definitive radiotherapy versus surgery and radiotherapy for stages I-III were 52% and 89% and for stage IV they were 46% and 58%, respectively. The 5-year cause-specific survival rates after definitive radiotherapy compared with surgery and radiotherapy for stages I-III were 57% and 82% and for stage IV they were 45% and 43%, respectively. Multivariate analyses revealed that the likelihood of cure was better with surgery and radiotherapy compared with radiotherapy alone (p=0.041). CONCLUSION: Patients treated with surgery and radiotherapy had a better chance of cure than those treated with radiotherapy alone. Complications of treatment were common in both groups but more common in patients who underwent surgery.

Effects of Tongue Strength Training on Quality of Life in Head and Neck Cancer Patients: Results From a Pilot Interventional Clinical Trial.

BACKGROUND: Head and neck cancer (HNC) patients often have dysphagia following surgical and/or chemoradiation treatment, which can lead to reduced quality of life. Some patients suffer from decreased tongue strength and mobility that may cause discomfort and difficulty with swallowing. Our group has developed a patented genioglossus muscle strength trainer (GMST) to increase tongue protrusive force that has been used in patients with sleep apnea. We hypothesized that the GMST device would increase tongue strength in the HNC population. METHODS: We conducted an IRB approved, non-randomized, interventional clinical trial of HNC patients with dysphagia to determine the effect of GMST on tongue strength. Our secondary objective was to assess dysphagia quality of life, as determined by questionnaires. Genioglossus muscle strength measurements (measured in Newtons, N) and dysphagia quality of life scores (SWAL-QoL questionnaire) were obtained from enrolled patients at baseline and following 4 weeks of intervention. Treatment was at-home GMST exercise regimen 3 times daily, 5 days per week. Compliance was assessed via review of training logs. Two-sided paired t-tests at significance level α = .05 were performed to assess difference in mean GG muscle strength pre- and post-treatment. RESULTS: Out of 10 patients initially enrolled, 7 patients completed the trial. Eighty-six percent were male and the average age was 60. About 5 patients had surgery plus adjuvant radiation and 2 patients had primary radiation. All patients had baseline dysphagia as determined by patient complaint and/or objective measurement (prior modified barium swallow). No adverse events were reported. We observed a statistically significant increase in genioglossus muscle strength (mean change: 4.0 N, 95% CI 1.1-6.9, P = .015) after 4 weeks of treatment. Patients reported reduced swallowing burden and feeling of stigma around eating based on SWAL-QoL results. CONCLUSIONS: Our data suggest that protrusive tongue-training exercises utilizing a novel tongue trainer device is well-tolerated and increases genioglossus muscle strength in treated HNC patients complaining of dysphagia. Patient-reported outcomes based on the SWAL-QoL survey indicate improvements in quality-of-life post-treatment, although our results are limited by small sample size. Larger studies are needed to see if this device could have clinically meaningful results for this difficult-to-treat patient population.

Practical Considerations for the Treatment of an Adrenal Metastasis With Stereotactic Body Radiation Therapy.

The purpose of this paper is to summarize 3 methods for treating adrenal metastases with stereotactic body radiation therapy. This article is not meant to provide consensus guidelines but rather to present 4 practical examples of treatment techniques using different treatment platforms from 3 institutions.

Infant versus noninfant formulas and cow's milk: Transition based on age or weight?

Infant formulas are meant to be used until 1 year of age, at which point children are transitioned to non-infant formulas or cow's milk, depending on their remaining dietary intake. Noninfant formulas and cow's milk are appropriate for children who have an average weight at that 1-year mark (9-9.5 kg); however, can contribute significant protein and/or electrolytes to children who are underweight for age, particularly if they still rely heavily on formula feeding for their caloric intake. In this short communication, we present several cases of patients who received excessive amounts of nutrients for age following the formula transition at the 1-year mark. We also provide recommendations for clinicians to consider when faced with underweight infants who are meant to be transitioning off infant formulas.

Flap Reconstruction Results in Longer Overall Treatment Time in Patients Treated With Surgery and Adjuvant Radiotherapy for Carcinoma of the Oral Cavity and Larynx.

OBJECTIVE: There is an inverse relationship between cancer cure and overall treatment time (OTT) in patients treated with surgical resection and radiotherapy (RT). METHODS: OTT was evaluated based on the reconstruction procedure in 420 patients with oral cavity and larynx cancers treated with surgery and RT between 1991 and 2020. RESULTS: With OTT >85 days, the difference between no versus yes flap reconstruction was ~20 percentage points and significant for all comparisons: primary closure (+/- skin graft), 49%, vs. rotation or free flap, 71% ( P <0.0001); primary closure (+/- skin graft), 49%, versus free flap without bone, 66% ( P =0.0358); and primary closure (+/- skin graft), 49%, versus free flap with bone, 82% ( P <0.0001). CONCLUSIONS: The use of flap reconstructions results in substantial increases in OTT. Findings suggest a need to reevaluate current policies regarding the choice of reconstruction and starting RT sooner after surgery.

Consideration of Metastasis-Directed Therapy for Patients With Metastatic Colorectal Cancer: Expert Survey and Systematic Review.

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.

Oligometastatic Colorectal Cancer: A Review of Definitions and Patient Selection for Local Therapies.

PURPOSE: Nearly one-third of patients diagnosed with colorectal cancer (CRC) will ultimately develop metastatic disease. While a small percentage of patients can be considered for curative resection, more patients have limited disease that can be considered for local therapy. Challenges remain in defining oligometastatic CRC as well as developing treatment strategies guided by high level evidence. METHODS: In this review, we present the challenges in defining oligometastatic CRC and summarize the current literature on treatment and outcomes of local therapy in patients with metastatic CRC. RESULTS: For patients with liver- and/or lung-confined CRC metastases, surgical resection is the standard of care given the potential for long-term progression-free and overall survival. For patients with liver- or lung-confined disease not amenable to surgical resection, non-surgical local therapies, such as thermal ablation, hepatic arterial infusion pump (HAIP), or stereotactic body radiation therapy (SBRT), should be considered. For patients with more advanced disease, such as lymph node or bony metastases, the role of metastasis-directed therapy is controversial. Emerging data suggests that SBRT to ablate all metastases can improve progression-free and overall survival. CONCLUSION: Multidisciplinary management is critical for patients with metastatic CRC due to the complexity of their cases and the nuanced patient, tumor, biological, and anatomical factors that must be weighed when considering local therapy. High-quality prospective randomized data in CRC are needed to further clarify the role of local ablative therapy in patients with unresectable oligometastatic CRC with ongoing studies including the RESOLUTE trial (ACTRN12621001198819) and the upcoming NCTN ERASur trial (NCT05673148).

Does lymphovascular invasion predict survival in oral cancer? A population-based analysis.

OBJECTIVE: To evaluate lymphovascular invasion as an independent predictor for overall survival in patients with oral cavity squamous cell carcinoma. STUDY DESIGN: Retrospective cohort study. SETTING: Multi-center, population-based facilities reporting to the National Cancer Database registry. METHODS: The database was accessed to collect data on patients with oral cavity squamous cell carcinoma. A multivariate cox proportional hazards model was used to analyze the association between presence of lymphovascular invasion and overall survival. RESULTS: 16,992 patients met inclusion criteria. 3,457 patients had lymphovascular invasion. The mean follow-up was 32 ± 19 months. Lymphovascular invasion predicted reduced 2-year overall survival (relative hazard 1.29, 95% CI: 1.20, 1.38, p < 0.001) and 5-year overall survival (relative hazard 1.30, 95% CI: 1.23, 1.39, p < 0.001). LVI reduced overall survival in patients with squamous cell carcinoma of the oral tongue (HR: 1.27, 95% CI: 1.17, 1.39, p < 0.001), floor of mouth (HR: 1.33, 95% CI: 1.17, 1.52, p < 0.001) and buccal mucosa (HR: 1.44, 95% CI: 1.15, 1.81, p = 0.001). Patients with lymphovascular invasion treated with surgery plus post-operative radiotherapy had significantly improved survival compared to those who underwent surgery alone (relative hazard 1.79, 95% CI: 1.58, 2.03, p < 0.001), and patients treated with surgery + post-operative chemoradiotherapy had improved survival compared to those treated with surgery alone (relative hazard 2.0, 95% CI: 2.26, 1.79, p < 0.001). CONCLUSION: Lymphovascular invasion is an important independent risk factor for decreased overall survival in oral cavity squamous cell carcinoma involving the oral tongue, floor of mouth and buccal mucosa subsites.

Tumor volume as a predictor of survival in advanced laryngeal cancer treated with total laryngectomy.

BACKGROUND: Recent literature shows that tumor volume (TV) in T3 laryngeal squamous cell carcinoma (LSCC) is associated with response to radiation therapy. The aim of this study was to evaluate the effect of TV on survival outcomes in patients undergoing total laryngectomy (TL). METHODS: One hundred and seventeen patients with LSCC undergoing TL between 2013 and 2020 at the University of Florida were included. TV was measured using a previously validated method on preoperative-CT scans. Multivariable CoxPH models for overall survival (OS) and disease-specific survival (DSS), metastasis-free survival (MFS), and recurrence-free survival (RFS) were developed with TV. RESULTS: Mean age was 61.5 years and 81.2% were male. Higher TV was associated with decreased OS, MFS, DSS, and RFS with adjusted hazard ratios 1.02 (95%CI: 1.01, 1.03), 1.01, (95%CI: 1.00, 1.03), 1.03 (95%CI: 1.01, 1.06), and 1.02 (95%CI: 1.00, 1.03) respectively. TV >7.1 cc had worse prognoses. CONCLUSIONS: TV appears associated with decreased survival in LSCC treated with TL.

The room where it happens: addressing diversity, equity, and inclusion in National Clinical Trials Network clinical trial leadership.

Many multicenter randomized clinical trials in oncology are conducted through the National Clinical Trials Network (NCTN), an organization consisting of 5 cooperative groups. These groups are made up of multidisciplinary investigators who work collaboratively to conduct trials that test novel therapies and establish best practice for cancer care. Unfortunately, disparities in clinical trial leadership are evident. To examine the current state of diversity, equity, and inclusion across the NCTN, an independent NCTN Task Force for Diversity in Gastrointestinal Oncology was established in 2021, the efforts of which serve as the platform for this commentary. The task force sought to assess existing data on demographics and policies across NCTN groups. Differences in infrastructure and policies were identified across groups as well as a general lack of data regarding the composition of group membership and leadership. In the context of growing momentum around diversity, equity, and inclusion in cancer research, the National Cancer Institute established the Equity and Inclusion Program, which is working to establish benchmark data regarding diversity of representation within the NCTN groups. Pending these data, additional efforts are recommended to address diversity within the NCTN, including standardizing membership, leadership, and publication processes; ensuring diversity of representation across scientific and steering committees; and providing mentorship and training opportunities for women and individuals from underrepresented groups. Intentional and focused efforts are necessary to ensure diversity in clinical trial leadership and to encourage design of trials that are inclusive and representative of the broad population of patients with cancer in the United States.

Alliance for Clinical Trials in Oncology (Alliance) trial A022101/NRG-GI009: A pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur).

Background: For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. Methods: The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. Discussion: The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC.

Local Therapies in Advanced Colorectal Cancer.

Curative intent surgical resection of colorectal metastases to the liver and lungs in eligible patients results in improved disease control and prolonged overall survival with the potential for cure in a subset of patients. Additional ablative and local therapies for use in the liver, lungs, and other body sites have been developed with emerging data on the utility and toxicity of these treatments. Future studies should focus on identification of appropriate candidates for treatment and determining the optimal modality and timing of treatment accounting for both patient and disease factors.