Background and Objectives: Guidelines for Stage II colon cancer recommend adjuvant chemotherapy (AC) only for tumors with high-risk features, but long-term outcomes data are mixed. We aimed to determine if AC was associated with a survival benefit in this population.Methods: Patients were identified from the National Cancer Database and included if they met the following criteria: diagnosis of Stage II colon cancer, surgery, survival data, and complete data on six high-risk features. The cohort of 57 335 patients was stratified by receipt of AC. Subgroup analysis was performed on patients under the age of 65 years with no comorbidities. Overall survival (OS) was the primary endpoint.Results: An increasing number of high-risk features was associated with significantly decreased median OS. AC was associated with significantly increased OS for patients with 0, 1, 2, and ≥3 high-risk features. On subgroup analysis, receipt of AC was associated with a reduced risk of death (hazard ratio: 0.66; confidence interval: 0.59-0.74). For patients in the subgroup who had a T4 tumor, AC was associated with increased OS (92.7 vs. 83.6 months).Conclusions: AC should be considered for all younger, healthy patients with Stage II colon cancer and may be associated with a survival benefit for patients with T4 disease. K E Y W O R D S adjuvant chemotherapy, colon cancer, high risk, NCDB, Stage II 1 | INTRODUCTION Colorectal cancer remains the third most common malignancy and the second most common cause of cancer-related death worldwide. 1 Decades of research have led to advancements in understanding colorectal cancer pathophysiology, resulting in better treatment options and screening strategies. As a result, in the United States, annual mortality for colorectal cancer has steadily declined.Globally, however, colorectal cancer continues to be a leading cause of cancer death. 2 In 2020, colorectal cancer reached 10% worldwide incidence and accounted for 9.4% of total cancer-related mortality. 3 Ninety percent of colorectal cancer is diagnosed in patients 50 years and older. However, more recent data indicate a rising incidence and mortality rate for patients under the age of 50 years. 4,5

OBJECTIVE Stereotactic radiosurgery (SRS) of the spine is a conformal method of delivering a high radiation dose to a target in a single or few (usually ≤ 5) fractions with a sharp fall-off outside the target volume. Although efforts have been focused on evaluating spinal cord tolerance when treating spinal column metastases, no study has formally evaluated toxicity to the surrounding organs at risk (OAR), such as the brachial plexus or the oropharynx, when performing SRS in the cervicothoracic region. The aim of this study was to evaluate the radiation dosimetry and the acute and delayed toxicities of SRS on OAR in such patients. METHODS Fifty-six consecutive patients (60 procedures) with a cervicothoracic spine tumor involving segments within C5–T1 who were treated using single-fraction SRS between February 2006 and July 2014 were included in the study. Each patient underwent CT simulation and high-definition MRI before treatment. The clinical target volume and OAR were contoured on BrainScan and iPlan software after image fusion. Radiation toxicity was evaluated using the common toxicity criteria for adverse events and correlated to the radiation doses delivered to these regions. The incidence of vertebral body compression fracture (VCF) before and after SRS was evaluated also. RESULTS Metastatic lesions constituted the majority (n = 52 [93%]) of tumors treated with SRS. Each patient was treated with a median single prescription dose of 16 Gy to the target. The median percentage of tumor covered by SRS was 93% (maximum target dose 18.21 Gy). The brachial plexus received the highest mean maximum dose of 17 Gy, followed by the esophagus (13.8 Gy) and spinal cord (13 Gy). A total of 14 toxicities were encountered in 56 patients (25%) during the study period. Overall, 14% (n = 8) of the patients had Grade 1 toxicity, 9% (n = 5) had Grade 2 toxicity, 2% (n = 1) had Grade 3 toxicity, and none of the patients had Grade 4 or 5 toxicity. The most common (12%) toxicity was dysphagia/odynophagia, followed by axial spine pain flare or painful radiculopathy (9%). The maximum radiation dose to the brachial plexus showed a trend toward significance (p = 0.066) in patients with worsening post-SRS pain. De novo and progressive VCFs after SRS were noted in 3% (3 of 98) and 4% (4 of 98) of vertebral segments, respectively. CONCLUSIONS From the analysis, the current SRS doses used at the Cleveland Clinic seem safe and well tolerated at the cervicothoracic junction. These preliminary data provide tolerance benchmarks for OAR in this region. Because the effect of dose-escalation SRS strategies aimed at improving local tumor control needs to be balanced carefully with associated treatment-related toxicity on adjacent OAR, larger prospective studies using such approaches are needed.

Nonalcoholic fatty liver disease (NAFLD) is a disease spectrum that spans simple steatosis, fibrosis, and ultimately cirrhosis, and is a leading cause of chronic liver disease globally. The severe variant of NAFLD, non-alcoholic steatohepatitis (NASH), is characterized by triglyceride accumulation within hepatocytes and the subsequent inflammatory pathway activation, ultimately progressing to cirrhosis in 10%-20% of patients. NASH is a known major risk factor for the development of hepatocellular carcinoma (HCC), and there is emerging data demonstrating the impact of NASH on immune subsets and the tumor microenvironment that may influence therapeutic response. This review describes the various ways in which the immune system is altered in patients with NASH. The innate immune system in NASH shows alterations in dendritic and Kupffer cells, impaired cytotoxicity of Natural Killer cells, and an accumulation of neutrophils. Additionally, there is emerging evidence emphasizing the role of the adaptive immune system in the development and progression of NASH, seen in the alteration of B-cells, T-cells, and NKT Cells. Due to the complex interplay of the immune system in NAFLD/NASH and its progression to HCC, many current treatments focus on targeting immune cells for HCC therapy. Recently, immune checkpoint inhibitors such as atezolizumab and bevacizumab have been approved as first-line therapy for unresectable HCC. Although an emerging field of research, further studies and clinical trials are needed to understand the complex interface of NASH, HCC and the immune response.

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